阅读说明：本技术 环形rna在系统性红斑狼疮制备治疗药物中的应用 (Application of circular RNA in preparation of therapeutic drugs for systemic lupus erythematosus ) 是由 陈玲玲 杨力 刘楚霄 李响 南芳 于 2019-02-25 设计创作，主要内容包括：本发明属于生物医学领域,具体涉及具有长度是16bp-33bp的不完整双链结构的环形RNA和/或具有长度是16bp-33bp的不完整双链结构的环形RNA在系统性红斑狼疮制备治疗药物中的应用。所述具有长度是16bp-33bp的不完整双链结构的环形RNA基因作为诊断系统性红斑狼疮的标志物,使系统性红斑狼疮的诊断更加准确、快速。所述环形RNA其基因表达产物作为制备治疗系统性红斑狼疮的药物分子,为治疗系统性红斑狼疮提供了新的治疗途径。(The invention belongs to the field of biomedicine, and particularly relates to application of circular RNA with an incomplete double-chain structure with the length of 16bp-33bp and/or circular RNA with an incomplete double-chain structure with the length of 16bp-33bp in preparation of a therapeutic drug for systemic lupus erythematosus. The circular RNA gene with the incomplete double-chain structure with the length of 16bp-33bp is used as a marker for diagnosing the systemic lupus erythematosus, so that the diagnosis of the systemic lupus erythematosus is more accurate and rapid. The gene expression product of the circular RNA is used for preparing a drug molecule for treating systemic lupus erythematosus, and a new treatment way is provided for treating systemic lupus erythematosus.)

1. Use of circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or a promoter of circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp in the preparation of a therapeutic agent for systemic lupus erythematosus.

2. The use of claim 1, further comprising one or more of the following features:

1) the circular RNA having an incomplete double-stranded structure with a length of 16bp-33bp is selected from one or more of circARID1B, circCAMSAP1, circCCNB1, circCNN2, circDHX34, circEPHB4, circEZH2, circFCHO2, circFGFR1, circFKBP8, circKIAA0368, circMBOAT2, circPIP5K1C, circPOLR2 LR2A, circSNPPP 1 PPP1CB, circPROSC, circPTK2, circPVT1, circRELL1, circSDHAF2, circSLC22A23, circSNHG4, circCD, circEM 181, circEMC 1, and circVAC;

2) the circular RNA promoter having an incomplete double-stranded structure of 16bp-33bp in length is selected from one or more of a circARID1B promoter, a circCAMSAP1 promoter, a circCCNB1 promoter, a circCNN2 promoter, a circDHX34 promoter, a circEPHB4 promoter, a circEZH2 promoter, a circFCHO2 promoter, a circFGFR1 promoter, a circFKBP8 promoter, a circKIAA0368 promoter, a circMBOAT2 promoter, a circPIP5K1C promoter, a circPOLR2A promoter, a circPPP1CB promoter, a circPROSC promoter, a circPTK2 promoter, a circPVT1 promoter, a circRELL1 promoter, a circSDHAF2 promoter, a circSLC22A23 promoter, a circSNPB 4 promoter, a circPECS promoter, a CIRCEM 181D promoter, a TMTMTMHG promoter, a promoter, and a TMVAHG 1 promoter.

3. The use of claim 1, wherein the systemic lupus erythematosus treatment drug has at least one of the following utilities: (1) reducing PKR phosphorylation in monocytes of a patient with systemic lupus erythematosus; (2) the expression level of cell factor IFN-beta and systemic lupus erythematosus diagnosis gene MX-1, LY-6E and IFIT3 in mononuclear cells and immune cell T cells of systemic lupus erythematosus patients is reduced.

4. The use according to claim 1, wherein the promoter of a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp is a substance that increases the level of a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33 bp.

5. The use according to claim 4, characterized in that the level of circular RNA having a incomplete double-stranded structure with a length of 16bp-33bp is increased by means of over-expressing circular RNA having a incomplete double-stranded structure with a length of 16bp-33 bp.

6. The use according to claim 1, wherein the promoter for the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp is the only active ingredient or one of the active ingredients of the therapeutic agent for systemic lupus erythematosus.

7. A systemic lupus erythematosus therapeutic drug comprises an effective dose of a promoter for circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or circular RNA having an incomplete double-stranded structure with a length of 16bp to 33 bp.

8. The therapeutic agent for systemic lupus erythematosus of claim 7 further comprising one or more of the following characteristics:

1) the circular RNA having an incomplete double-stranded structure with a length of 16bp-33bp is selected from one or more of circARID1B, circCAMSAP1, circCCNB1, circCNN2, circDHX34, circEPHB4, circEZH2, circFCHO2, circFGFR1, circFKBP8, circKIAA0368, circMBOAT2, circPIP5K1C, circPOLR2 LR2A, circSNPPP 1 PPP1CB, circPROSC, circPTK2, circPVT1, circRELL1, circSDHAF2, circSLC22A23, circSNHG4, circCD, circEM 181, circEMC 1, and circVAC;

2) the circular RNA promoter having an incomplete double-stranded structure of 16bp-33bp in length is selected from one or more of a circARID1B promoter, a circCAMSAP1 promoter, a circCCNB1 promoter, a circCNN2 promoter, a circDHX34 promoter, a circEPHB4 promoter, a circEZH2 promoter, a circFCHO2 promoter, a circFGFR1 promoter, a circFKBP8 promoter, a circKIAA0368 promoter, a circMBOAT2 promoter, a circPIP5K1C promoter, a circPOLR2A promoter, a circPPP1CB promoter, a circPROSC promoter, a circPTK2 promoter, a circPVT1 promoter, a circRELL1 promoter, a circSDHAF2 promoter, a circSLC22A23 promoter, a circSNPB 4 promoter, a circPECS promoter, a CIRCEM 181D promoter, a TMTMTMHG promoter, a promoter, and a TMVAHG 1 promoter.

9. A systemic lupus erythematosus therapeutic drug combination comprises effective dose of circular RNA with a length of 16bp-33bp incomplete double-chain structure and/or promoter of circular RNA with a length of 16bp-33bp incomplete double-chain structure, and at least one other systemic lupus erythematosus therapeutic drug.

10. Use of a promoter for a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp for the preparation of a medicament having any one or more of the following effects: (1) reducing PKR phosphorylation in monocytes of a patient with systemic lupus erythematosus; (2) the expression level of cell factor IFN-beta and systemic lupus erythematosus diagnosis gene MX-1, LY-6E and IFIT3 in mononuclear cells (PBMC) and immune cell T cells of a systemic lupus erythematosus patient is reduced.

11. Use of circular RNA with incomplete double-stranded structure with length of 16bp-33bp in preparation or screening of systemic lupus erythematosus treatment drugs.

12. Use of circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp for preparing or screening a systemic lupus erythematosus detection reagent.

13. The application of the reagent for specifically recognizing the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp in the preparation of the systemic lupus erythematosus detection kit.

14. A systemic lupus erythematosus detection kit at least comprises a reagent for specifically recognizing a circular RNA with a length of 16bp-33bp of an incomplete double-stranded structure.

Technical Field

The invention belongs to the field of biomedicine, and particularly relates to application of circular RNA in preparation of a therapeutic drug for systemic lupus erythematosus.

Background

Systemic Lupus Erythematosus (SLE) is a typical multi-organ, multi-system autoimmune disease, and its clinical and immunological phenotypes are extremely complex and diverse, including immune tolerance deficiency, lymphocyte function regulation and apoptosis disorder, complement deficiency and immune complex clearance disorder, cytokine secretion regulation disorder, etc., and almost cover the whole immune system disorder. Clinically, it is manifested as damage to various organs such as kidney, nervous system, mental system, and blood system. If early diagnosis can be performed before the SLE patient is affected by important organs, the method has great significance for preventing and treating SLE, improving the life quality of the patient and improving the productivity of the patient. However, the markers currently used for biological diagnosis are mostly biochemical and immunological changes occurring after organ damage, and do not allow early diagnosis of organ involvement in SLE patients.

Currently, the etiology and pathogenesis of SLE are not completely clear, and are influenced by many aspects such as family inheritance, sex hormone disorder, environmental factors and the like. Therefore, specific treatment means is still lacked, and the prevention and treatment level of the disease cannot be fundamentally improved.

Disclosure of Invention

In order to overcome the problems in the prior art, the invention aims to research the expression of the circular RNA in the systemic lupus erythematosus and the mediation effect of the circular RNA on the biological function of the systemic lupus erythematosus, and provides the application of an expression product based on the circular RNA in the aspect of diagnosis and treatment of the systemic lupus erythematosus.

In order to achieve the above objects and other related objects, the present invention adopts the following technical solutions:

in the first aspect of the present invention, there is provided a use of a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or an enhancer for a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp for the preparation of a therapeutic agent for systemic lupus erythematosus.

In a second aspect of the present invention, there is provided a method for treating systemic lupus erythematosus, comprising administering to a subject an effective amount of an agent for promoting the administration of a circular RNA having an incomplete double-stranded structure of 16bp to 33bp in length and/or a circular RNA having an incomplete double-stranded structure of 16bp to 33bp in length.

In a third aspect of the present invention, there is provided a systemic lupus erythematosus therapeutic agent comprising an effective amount of a circular RNA having an incomplete double-stranded structure of 16bp to 33bp in length and/or an enhancer of a circular RNA having an incomplete double-stranded structure of 16bp to 33bp in length.

In a fourth aspect of the present invention, there is provided a therapeutic drug combination for systemic lupus erythematosus, comprising an effective amount of a promoter for a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp, and at least one other therapeutic drug for systemic lupus erythematosus.

In the fifth aspect of the present invention, a method for treating systemic lupus erythematosus is provided, wherein an effective amount of a promoter for administering to a subject a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp, and an effective amount of another systemic lupus erythematosus treatment drug and/or another systemic lupus erythematosus treatment means to a subject are administered.

In a sixth aspect of the present invention, there is provided a use of a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or an enhancer for a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp for the preparation of a medicament having any one or more of the following effects:

(1) modulating the circular RNA pathway to increase the circular RNA level;

(2) directly increasing the level of the circular RNA in the cell.

The seventh aspect of the invention provides the use of the circular RNA having an incomplete double-stranded structure with a length of 16bp-33bp and/or the promoter of the circular RNA having an incomplete double-stranded structure with a length of 16bp-33bp in the preparation or screening of systemic lupus erythematosus treatment drugs.

In the eighth aspect of the present invention, the use of circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp for preparing or screening a systemic lupus erythematosus detection reagent is provided.

The ninth aspect of the present invention provides a use of a reagent for specifically recognizing a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp in the preparation of a systemic lupus erythematosus detection kit.

The tenth aspect of the present invention provides a systemic lupus erythematosus detection kit, which at least includes a reagent that specifically recognizes a circular RNA having an incomplete double-stranded structure with a length of 16bp to 33 bp.

Compared with the prior art, the invention has the following beneficial effects:

the invention detects the expression of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp by designing a pair of specific primers; then, the invention finds that the expression level is obviously reduced by detecting the expression condition of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp in the systemic lupus erythematosus patient, thereby being used as a diagnostic marker of the systemic lupus erythematosus. In addition, the invention carries out in vitro cell functional research on the circular RNA gene with the incomplete double-stranded structure with the length of 16bp-33bp, and constructs an expression vector for over-expressing the circular RNA gene with the incomplete double-stranded structure with the length of 16bp-33bp by constructing the circular RNA gene sequence on an pZW1 vector. Compared with a control transfected with an empty vector, the phosphorylation level of phosphorylation kinase PKR of the mononuclear cells of the systemic lupus erythematosus patient overexpressing the circular RNA gene with the incomplete double-chain structure with the length of 16bp-33bp is obviously reduced, and the expression quantity of cytokines IFN-beta and systemic lupus erythematosus diagnostic genes in the mononuclear cells (PBMC) of the systemic lupus erythematosus patient and immune cell T cells is reduced. The circular RNA gene with the incomplete double-chain structure with the length of 16bp-33bp and the expression product thereof can be applied to the preparation of the medicine for treating the systemic lupus erythematosus. In conclusion, the circular RNA gene with the incomplete double-chain structure with the length of 16bp-33bp is used as a marker for diagnosing the systemic lupus erythematosus, so that the diagnosis of the systemic lupus erythematosus is more accurate and rapid. The gene expression product of the circular RNA is used for preparing a drug molecule for treating systemic lupus erythematosus, and a new treatment way is provided for treating systemic lupus erythematosus.

Drawings

FIG. 1: is a map of the position of circPOLR2A on the chromosome.

FIG. 2: in order to detect the expression level of the circPOLR2A in the systemic lupus erythematosus patient by using a specific detection primer.

FIG. 3: the receiver operating characteristic curve (ROC curve) obtained using circular RNA circPOLR 2A.

FIG. 4: schematic diagram of secondary structures of circPOLR2A, 25 circular RNAs with special double-stranded structure in the same class, and circSMARCA5 without special double-stranded structure.

FIG. 5: after overexpression of circPOLR2A and circular RNA circSMARCA5 without a special double-stranded structure, the phosphorylation levels of PKR and PKR downstream genes are detected.

FIG. 6: after the circPOLR2A is over-expressed, the phosphorylation level of PKR is detected, and the expression quantity of cytokines IFN-beta and systemic lupus erythematosus diagnostic genes MX-1, LY-6E and IFIT3 in mononuclear cells (PBMC) and immune cell T cells of a systemic lupus erythematosus patient is reduced.

Detailed Description

Before the present embodiments are further described, it is to be understood that the scope of the invention is not limited to the particular embodiments described below; it is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention. Test methods in which specific conditions are not specified in the following examples are generally carried out under conventional conditions or under conditions recommended by the respective manufacturers.

When numerical ranges are given in the examples, it is understood that both endpoints of each of the numerical ranges and any value therebetween can be selected unless the invention otherwise indicated. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In addition to the specific methods, devices, and materials used in the examples, any methods, devices, and materials similar or equivalent to those described in the examples may be used in the practice of the invention in addition to the specific methods, devices, and materials used in the examples, in keeping with the knowledge of one skilled in the art and with the description of the invention.

Unless otherwise indicated, the experimental methods, detection methods, and preparation methods disclosed herein all employ techniques conventional in the art of molecular biology, biochemistry, chromatin structure and analysis, analytical chemistry, cell culture, recombinant DNA technology, and related arts.

Circular RNA (circRNAs) is a newly discovered class of non-coding RNA molecules. Unlike conventional linear RNA, circular RNA does not have a5 'terminal cap and a 3' terminal poly (a) tail, and forms a closed circular structure with covalent bonds. Recent studies indicate that circular RNA is mainly generated through reverse-splicing (back-splicing), widely exists in various biological cells, has extremely high structural stability, is difficult to be degraded by exonuclease (exonuclease), and has the characteristics of tissue and space-time specificity in expression. These characteristics make circRNA have wide prospects in the development and application of disease diagnosis and treatment methods.

The embodiment of the invention provides application of a circular RNA with an incomplete double-chain structure with the length of 16bp-33bp and/or an accelerant of a circular RNA with an incomplete double-chain structure with the length of 16bp-33bp in preparation of a systemic lupus erythematosus treatment drug. The incomplete double-stranded structure is defined as a stem-loop double-stranded structure formed by RNA, wherein perfect complementary paired bases exist and internal loops (bulges) or internal loops (internal loops) formed by unpaired bases also exist. The incomplete double-stranded structure is calculated by the number of complementary paired bases, and if the number of non-paired bases in which a bulge or an internal loop occurs but in which the bulge or the internal loop is less than or equal to 4, the incomplete double-stranded structure is considered to be still an incomplete double-stranded structure rather than a plurality of incomplete double-stranded structures.

The circular RNA having a special double-stranded structure and the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp described in the present invention refer to the same substance.

The circular RNAs with incomplete double-stranded structure of length 16bp-33bp as described in the examples of the present invention are each selected from any one or more of circARID1B, circCAMSAP1, circCCNB1, circCNN2, circDHX34, circEPHB4, circEZH2, circFCHO2, circFGFR1, circFKBP8, circKIAA0368, circMBOAT2, circPIP5K1C, circPOLR2A, circPPP1CB, circPROSC, circPTK2, circPVT1, circRELL1, circSDHAF2, circSLC22A23, circSNHG4, circTBCD, circTMEM181, circUIMC1, and circVAcPB.

The promoters of circular RNA having an incomplete double-stranded structure with a length of 16bp-33bp described in the examples of the present invention are each selected from the group consisting of circARID1B promoter, circCAMSAP1 promoter, circCCNB1 promoter, circCNN2 promoter, circDHX34 promoter, circEPHB4 promoter, circEZH2 promoter, circFCHO2 promoter, circFGFR1 promoter, circFKBP8 promoter, circKIAA0368 promoter, circMBOAT2 promoter, circPIP5K1C promoter, circLR 2A promoter, circPPP1CB promoter, circPROSC promoter, circPTK2 promoter, circPVrcT 1 promoter, circRELL1 promoter, circSDHAF 84 promoter, circSPSLC 22A23 promoter, circSNPB 4 promoter, circSND promoter, circEMG 181 promoter, circEMC 1 promoter, and one or more promoters of the CIRCTMTBCM 3745.

The circular RNA has the following specific information:

circARID1B (data baseID: HSA _ CIRCPEdia _54093), whose positioning on the genome is: chromosome 6, chr6:157,357,968-157,406,039, the corresponding linear gene was ARID1B (chr6:157,256,600-157,473,538), and the circular sequence was 286 bases and comprised the 2 nd and 3 rd exons of the ARID1B gene.

circcamap 1(data base id: HSA _ circcpedia _63397), whose genomic orientation is: chromosome 9, chr9:13,8773,478-138,774,924, the corresponding linear gene is CAMSAP1(chr9:138,700,333-138,799,005), the circular sequence has 425 bases, and comprises the 2 nd and 3 rd exons of CAMSAP1 gene.

circCCNB1(data baseID: HSA _ CIRCpDedia _52305), which is located on the genome as: chromosome 5, chr5:68,470,703-68,471,364, the corresponding linear gene is CCNB1(chr5:68,462,837-68,474,070), the circular sequence has 378 bases and comprises the 6 th and 7 th exons of the CCNB1 gene.

circCNN2(data baseID: HSA _ CIRCpDedia _ 2457), whose location on the genome is: chromosome 19, chr19:1,032,390-1,032,695, the corresponding linear gene is CNN2(chr19:1,026,274-1,039,067), and the circular sequence has 205 bases and comprises the 3 rd and 4 th exons of CNN2 gene.

circDHX34(data base ID: HSA _ CIRCpDedia _26297), whose positioning on the genome is: chromosome 19, chr19:47,865,732-47,865,950, where the corresponding linear gene is DHX34(chr19:47,852,538-47,885,961) and the circular sequence has 218 bases and includes exon 6 of DHX34 gene.

circEPHB4(data base ID: HSA _ CIRCpDedia _56001), its genomic orientation is: chromosome 7, chr7:100,410,368-100,410,830, the corresponding linear gene is EPHB4(chr7:100,400,187-100,423,148), the circularized sequence has 362 bases and comprises the 10 th and 11 th exons of EPHB4 gene.

circEZH2(data base ID: HSA _ CIRCpDedia _57174), whose location on the genome is: chromosome 7, chr7:148,543, 561-.

circFCHO2(data baseID: HSA _ CIRCPEdia _52515), its positioning on the genome is: chromosome 5, chr5:72,370,568-72,373,320, the corresponding linear gene was FCHO2(chr5:72,251,808-72,386,348), and the circular sequence had 268 bases and contained the 19 th and 20 th exons of the FCHO2 gene.

circFGFR1(data baseID: HSA _ CIRCPEdia _60993), its positioning on the genome is: chromosome 8, chr8:38,314,873-38,315,052, the corresponding linear gene being FGFR1(chr8:38,268,656-38,325,363), the circularized sequence having 179 bases and comprising the 2 nd exon of the FGFR1 gene.

circFKBP8(data base ID: HSA _ CIRCPEdia _25189), its positioning on the genome is: chromosome 19, chr19:18,650,180-18,650,530, the corresponding linear gene is FKBP8(chr19:18,642,561-18,654,387), the circularized sequence has 259 bases and comprises the 3 rd and 4 th exons of the FKBP8 gene.

circKIAA0368(data base ID: HSA _ CIRCpDedia _62244), whose location on the genome is: chromosome 9, chr9:114,148,656-114,154,104, the corresponding linear gene is KIAA0368(chr9:114,122,972-114,246,637), and the circular sequence has 435 bases and comprises 28 th, 29 th, 30 th and 31 th exons of KIAA0368 gene.

circMBOAT2(data base ID: HSA _ CIRCpDedia _42589), whose genomic orientation is: chromosome 2, chr2:9,083,315-9,098,771, the corresponding linear gene is MBOAT2(chr2:8,992,820-9,143,942), and the circular sequence has 224 bases and comprises the 2 nd and 3 rd exons of MBOAT2 gene.

CircPIP5K1C (data base ID: HSA _ CIRCPEdia _25726), its positioning on the genome is: chromosome 19 chr19:3,660,963-3,661,999, the corresponding linear gene is PIP5K1C (chr19:3,630,179-3,700,477), and the circular sequence has 249 bases and comprises the 4 th and 5 th exons of the PIP5K1C gene.

circPOLR2A (data baseID: HSA _ CIRCPEdia _22419), whose location on the genome is: chromosome 17, chr17:7,402,357-7,402,810, the corresponding linear gene is POLR2A (chr17:7,387,685-7,417,933), the circular sequence has 336 bases, and comprises the 9 th and 10 th exons of POLR2A gene.

circPPP1CB (data baseID: HSA _ CIRCPEdia _40659), whose positioning on the genome is: chromosome 2, chr2:29,006,772-29,011,675, the corresponding linear gene is PPP1CB (chr2:28,974,612-29,025,806), and the circular sequence has 224 bases and comprises the 5 th and 6 th exons of PPP1CB gene.

circPROSC (data base ID: HSA _ CIRCPEdia _60919), whose location on the genome is: chromosome 8, chr8:37,623,043-37,623,873, the corresponding linear gene is PROSC (chr8:37,620,101-37,637,286), and the circular sequence has 220 bases and comprises the 2 nd, 3 rd and 4 th exons of the PROSC gene.

circPTK2(data base ID: HSA _ CIRCPEdia _60281) whose positioning on the genome is: chromosome 8, chr8:141,889,569-141,900,868, the corresponding linear gene is PTK2(chr8:141,667,999-142,011,332), the circular sequence has 394 bases, including the 3 rd and 4 th exons of the PTK2 gene.

circPVT1(data base ID: HSA _ CIRCpDedia _60029), whose positioning on the genome is: chromosome 8, chr8:128,902,834-128,903,244, the corresponding linear gene is PVT1(chr8:128,806,779-129,113,499), the circularization sequence is 410 bases, and comprises the 2 nd exon of PVT1 gene.

circRELL1(data base ID: HSA _ CIRCPEdia _48457), whose location on the genome is: chromosome 4, chr4:37,633,006-37,640,126, the corresponding linear gene is RELL1(chr4:37,592,422-37,687,998), the circular sequence has 434 bases, and comprises the 4 th, 5 th and 6 th exons of the RELL1 gene.

circSDHAF2(data baseID: HSA _ CIRCPEdia _4841), whose genomic orientation is: chromosome 11, chr11:61,205,096-61,205,585, where the corresponding linear gene is SDHAF2(chr11:61,205,096-61,205,585), and the circular sequence has 334 bases, including the 2 nd and 3 rd exons of the SDHAF2 gene.

circSLC22A23(data baseID: HSA _ CIRCpDedia _54791), whose location on the genome is: chromosome 6, chr6:3,410,421-3,416,089, the corresponding linear gene is SLC22A23(chr6:3,269,196-3,457,256), and the circularization sequence has 259 bases and comprises the 2 nd and 3 rd exons of the SLC22A23 gene.

circSNHG4(data baseID: HSA _ CIRCpDedia _50464), whose genomic orientation is: chromosome 5, chr5:138,614,015-138,614,818, the corresponding linear gene is SNHG4(chr5:138,609,441-138,618,873), and the circular sequence has 161 bases and comprises the 3 rd and 4 th exons of the SNHG4 gene.

circTBCD (data base ID: HSA _ CIRCPEdia _22969), whose location on the genome is: chromosome 17 chr17:80,858, 526-.

circTMEM181(data base ID: HSA _ CIRCPedia _54188), its genomic orientation is: chromosome 6, chr6:159,004,985-159,010,814, the corresponding linear gene is TMEM181(chr6:158,957,468-159,049,522), and the circular sequence has 324 bases and comprises the 3 rd, 4 th and 5 th exons of the TMEM181 gene.

circUIMC1(data base ID: HSA _ CIRCPEdia _51249), whose location on the genome is: chromosome 5, chr5:176,370,335-176,385,155, the corresponding linear gene being UIMC1(chr5:176,332,006-176,433,409), the circular sequence having 397 bases and comprising the 7 th, 8 th, 9 th and 10 th exons of the UIMC1 gene.

circVAPB (data base ID: HSA _ CIRCPEdia _34824), whose location on the genome is: chromosome 20, chr20:57,014,000-57,016,139, the corresponding linear gene is VAPB (chr20:56,964,175-57,026,156), and the circular sequence has 258 bases and comprises the 4 th and 5 th exons of the VAPB gene.

In one embodiment, the systemic lupus erythematosus treatment agent has at least one of the following effects:

(1) reducing PKR phosphorylation in monocytes of a patient with systemic lupus erythematosus; (2) the expression level of cell factor IFN-beta and systemic lupus erythematosus diagnosis gene MX-1, LY-6E and IFIT3 in mononuclear cells and immune cell T cells of systemic lupus erythematosus patients is reduced.

The circular RNA promoter having an incomplete double-stranded structure with a length of 16bp to 33bp is a substance that increases the level of the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33 bp. Specifically, (1) the circARID1B promoter is a substance that increases the level of circARID 1B; (2) the circcamap 1 promoter is a substance that increases the level of circcamap 1; (3) the circCCNB1 promoter refers to a substance that increases the level of circCCNB 1; (4) the circCNN2 promoter is a substance which increases the level of circCNN 2; (5) a circDHX34 promoter refers to a substance that increases the level of circDHX 34; (6) the circEPHB4 promoter is a substance that increases the level of circEPHB 4; (7) the circEZH2 promoter refers to a substance that increases the level of circEZH 2; (8) a circFCHO2 promoter refers to a substance that increases the level of circFCHO 2; (9) the circFGFR1 promoter is a substance that increases the level of circFGFR 1; (10) a circFKBP8 promoter refers to a substance that increases the level of circFKBP 8; (11) the circKIAA0368 promoter is a substance for increasing the level of circKIAA 0368; (12) the circMBOAT2 promoter is a substance for increasing the level of circMBOAT 2; (13) the circPIP5K1C promoter is a substance which increases the level of circPIP5K 1C; (14) the circPOLR2A promoter is a substance for increasing the level of circPOLR 2A; (15) the circPPP1CB promoter is a substance that increases the circPPP1CB level; (16) circPROSC promoter refers to a substance that increases the level of circPROSC; (17) a circPTK2 promoter refers to a substance that increases the level of circPTK 2; (18) a circPVT1 promoter refers to a substance that increases the level of circPVT 1; (19) the circRELL1 promoter refers to a substance that increases the level of circRELL 1; (20) circSDHAF2 promoter refers to a substance that increases the level of circSDHAF 2; (21) the circSLC22a23 promoter is a substance that increases the level of circSLC22a 23; (22) the circSNHG4 promoter is a substance that increases the level of circSNHG 4; (23) a circTBCD promoter refers to a substance that increases the level of circTBCD; (24) the circTMEM181 promoter refers to a substance that increases the level of circTMEM 181; (25) circUIMC1 promoter refers to a substance that increases the level of circUIMC 1; (26) a circVAPB promoter refers to a substance that increases the level of circVAPB.

Specifically, the level of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp can adopt various chemical, physical and biological methods. Including but not limited to:

(1) adjusting the circular RNA pathway with the incomplete double-stranded structure with the length of 16bp-33bp to increase the level of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33 bp;

(2) the level of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp is directly increased in cells.

The level of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp can be directly increased by over-expressing the circular RNA with the incomplete double-stranded structure with the length of 16bp-33 bp.

Specifically, (1) circARID1B levels can be increased by overexpressing circARID 1B; (2) circcamap 1 levels can be increased by overexpressing circcamap 1; (3) the circCCNB1 levels can be increased by overexpressing circCCNB 1; (4) circCNN2 levels can be increased by overexpressing circCNN 2; (5) circDHX34 levels can be increased by overexpressing circDHX 34; (6) circEPHB4 levels can be increased by overexpressing circEPHB 4; (7) the circEZH2 levels can be increased by overexpressing circEZH 2; (8) circFCHO2 levels can be increased by means of overexpression of circFCHO 2; (9) circFGFR1 levels can be increased by means of overexpression of circFGFR 1; (10) the level of circFKBP8 can be increased by means of overexpression of circFKBP 8; (11) circKIAA0368 levels can be increased by overexpressing circKIAA 0368; (12) increases in circMBOAT2 levels by overexpressing circMBOAT 2; (13) circPIP5K1C levels may be increased by overexpressing circPIP5K 1C; (14) the circPOLR2A levels can be increased by overexpressing circPOLR 2A; (15) the circPPP1CB levels can be increased by overexpressing circPPP1 CB; (16) circPROSC levels can be increased by means of overexpression of circPROSC; (17) circPTK2 levels can be increased by overexpressing circPTK 2; (18) circPVT1 levels can be increased by means of overexpression of circPVT 1; (19) circRELL1 levels can be increased by overexpressing circRELL 1; (20) circSDHAF2 levels can be increased by overexpressing circSDHAF 2; (21) circSLC22a23 levels may be increased by overexpression of circSLC22a 23; (22) circSNHG4 levels can be increased by overexpressing circSNHG 4; (23) circTBCD levels can be increased by means of overexpression of circTBCD; (24) circTMEM181 levels can be increased by means of overexpression of circTMEM 181; (25) increases in circUIMC1 levels by overexpressing circUIMC 1; (26) circVAPB levels can be increased by means of overexpression of circVAPB.

The circular RNA passage with the incomplete double-stranded structure with the length of 16bp-33bp can be adjusted to be a circular RNA agonist with the incomplete double-stranded structure with the length of 16bp-33bp to increase the level of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33 bp.

Increasing the level of the circular RNA having the incomplete double-stranded structure with the length of 16bp to 33bp refers to increasing the circular RNA having the incomplete double-stranded structure with the length of 16bp to 33 bp. Preferably, the level of circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp is increased by at least 10%, preferably by at least 30%, more preferably by at least 50%, even more preferably by at least 70%, and most preferably by at least 90% as compared to the level of circular RNA having an incomplete double-stranded structure with a length of 16bp to 33 bp.

The embodiment of the invention proves that the PKR phosphorylation level of the mononuclear cells of a systemic lupus erythematosus patient is obviously reduced after the level of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp in the cells is directly increased by over-expressing the circular RNA with the incomplete double-chain structure with the length of 16bp-33 bp; the expression level of cell factor IFN-beta and systemic lupus erythematosus diagnosis gene MX-1, LY-6E and IFIT3 in mononuclear cells (PBMC) and immune cell T cells of a systemic lupus erythematosus patient is reduced. It is inferred that the method for regulating the circular RNA path with the incomplete double-stranded structure with the length of 16bp-33bp can also obtain the significant reduction of the PKR phosphorylation level of the mononuclear cells of the systemic lupus erythematosus patient; the expression level of cell factor IFN-beta and systemic lupus erythematosus diagnosis gene MX-1, LY-6E and IFIT3 in mononuclear cells (PBMC) and immune cell T cells of a systemic lupus erythematosus patient is reduced. It is further believed that these methods may also treat systemic lupus erythematosus.

The systemic lupus erythematosus treatment drug necessarily comprises the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp and/or the promoter of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp, and takes the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp and/or the promoter of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp as the effective component of the function.

In the systemic lupus erythematosus treating drug, the effective component exerting the functions can be only the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp and/or the promoter of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp, and can also comprise other molecules playing similar functions.

That is, the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or the promoter for the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp is the only active ingredient or one of the active ingredients of the systemic lupus erythematosus therapeutic agent.

The systemic lupus erythematosus treatment medicine can be a single-component substance or a multi-component substance.

The form of the systemic lupus erythematosus treatment drug is not particularly limited, and the systemic lupus erythematosus treatment drug can be in the forms of various substances such as solid, liquid, gel, semifluid, aerosol and the like.

The systemic lupus erythematosus treatment drug mainly aims at mammals such as rodents, primates and the like.

The method for treating systemic lupus erythematosus is to administer an effective amount of the accelerant of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp and/or the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp to a subject.

The subject may be a mammal. The mammal is preferably a rodent, artiodactyla, perissodactyla, lagomorpha, primate, or the like. The primate is preferably a monkey, ape or human.

The subject may be a patient suffering from systemic lupus erythematosus or an individual in whom prevention or alleviation of systemic lupus erythematosus is desired. Or can be isolated systemic lupus erythematosus cells from a patient suffering from systemic lupus erythematosus or from an individual in whom prevention or amelioration of systemic lupus erythematosus is desired.

The promoter for circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp can be administered to a subject before, during or after treatment for systemic lupus erythematosus.

The systemic lupus erythematosus treating medicine provided by the invention comprises effective dose of circular RNA with a length of 16bp-33bp incomplete double-chain structure and/or promoter of circular RNA with a length of 16bp-33bp incomplete double-chain structure.

In one embodiment, the therapeutic agent for systemic lupus erythematosus comprises an effective dose of the promoter for the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp and/or the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp and a medicinal carrier.

The systemic lupus erythematosus treatment drug necessarily comprises the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp and/or the promoter of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp, and takes the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp and/or the promoter of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp as the effective component of the function.

In the systemic lupus erythematosus treating medicine, the effective component exerting the functions can be only the promoter of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp and/or the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp, and can also comprise other molecules playing similar functions.

That is, the promoter for the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp and/or the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp is the only active ingredient or one of the active ingredients of the systemic lupus erythematosus-treating drug.

The systemic lupus erythematosus treatment medicine can be a single-component substance or a multi-component substance.

The form of the systemic lupus erythematosus treatment drug is not particularly limited, and the systemic lupus erythematosus treatment drug can be in the forms of various substances such as solid, liquid, gel, semifluid, aerosol and the like.

The systemic lupus erythematosus treatment drug mainly aims at mammals such as rodents, primates and the like.

The systemic lupus erythematosus treating medicine composition includes effective dose of circular RNA with incomplete double chain structure of 16bp-33bp and/or promoter of circular RNA with incomplete double chain structure of 16bp-33bp and at least one other systemic lupus erythematosus treating medicine.

The combination therapy drug combination may be in any one of the following forms:

firstly), the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp, the circular RNA accelerant with the incomplete double-chain structure with the length of 16bp-33bp and other systemic lupus erythematosus treatment medicines are respectively prepared into independent preparations, the preparation forms of the preparations can be the same or different, and the administration routes can be the same or different.

When the other therapeutic agent for systemic lupus erythematosus is an antibody, a parenteral administration type is generally employed. When other systemic lupus erythematosus treatment drugs are chemical drugs, the administration forms can be rich, and the administration can be gastrointestinal tract administration or parenteral tract administration. Known routes of administration for each chemical are generally recommended.

And secondly) the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp and/or the circular RNA promoter with the incomplete double-chain structure with the length of 16bp-33bp and other systemic lupus erythematosus treatment medicines are prepared into a compound preparation, and when the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp and/or the circular RNA promoter with the incomplete double-chain structure with the length of 16bp-33bp and other systemic lupus erythematosus treatment medicines are administrated by the same administration route and are applied at the same time, the circular RNA promoter and other systemic lupus erythematosus treatment medicines can be prepared into the compound preparation.

The method for treating systemic lupus erythematosus is to apply circular RNA with a length of 16bp-33bp incomplete double-chain structure and/or circular RNA promoter with a length of 16bp-33bp incomplete double-chain structure to a subject and to apply an effective amount of other systemic lupus erythematosus treatment medicines to the subject and/or apply other systemic lupus erythematosus treatment means to the subject.

The circular RNA having an incomplete double-stranded structure of 16bp to 33bp in length and/or the circular RNA promoter having an incomplete double-stranded structure of 16bp to 33bp in length, and at least one other systemic lupus erythematosus-treating agent may be administered in an effective amount simultaneously or sequentially.

Based on that the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp is the systemic lupus erythematosus treatment target which is discovered for the first time, the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp and/or the circular RNA promoter with the incomplete double-chain structure with the length of 16bp-33bp can at least play a role in adding curative effects in the combined use of other systemic lupus erythematosus treatment medicaments, and the treatment effect on the systemic lupus erythematosus is further enhanced.

Other systemic lupus erythematosus treatment drugs include but are not limited to: antibody drugs, chemical drugs or targeted drugs, etc.

The circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp and/or the circular RNA promoter with the incomplete double-stranded structure with the length of 16bp-33bp are used for gastrointestinal administration or parenteral administration. Other systemic lupus erythematosus treatment drugs may be gastrointestinal or parenteral.

The application of one or more of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp and/or the circular RNA promoter with the incomplete double-stranded structure with the length of 16bp-33bp provided by the embodiment of the invention in preparing the medicine with any one or more of the following functions:

(1) reducing PKR phosphorylation in monocytes of a patient with systemic lupus erythematosus; (2) the expression level of cell factor IFN-beta and systemic lupus erythematosus diagnosis gene MX-1, LY-6E and IFIT3 in mononuclear cells (PBMC) and immune cell T cells of a systemic lupus erythematosus patient is reduced.

The circular RNA with the incomplete double-chain structure with the length of 16bp-33bp provided by the embodiment of the invention is used for preparing or screening systemic lupus erythematosus treatment medicines.

In one embodiment the circular RNA with incomplete double-stranded structure with length of 16bp-33bp is used as the target of action. Specifically, one or more of circARID1B, circcamasp 1, circCCNB1, circCNN2, circDHX34, circEPHB4, circEZH2, circFCHO2, circFGFR1, circFKBP8, circKIAA0368, circMBOAT2, circPIP5K1C, circPOLR2A, circPPP1CB, circPROSC, circPTK2, circPVT1, circRELL1, circsdhad 2, circSLC22a23, circSNHG4, circd, circTMEM181, circUIMC1, and circVAPB are used as the action target.

The use specifically refers to: and screening candidate substances by taking the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp as an action object so as to find the promoter of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp as a candidate systemic lupus erythematosus treatment drug.

The promoter for the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp may be an overexpression agent for the circular RNA having an incomplete double-stranded structure with a length of 16bp to 33 bp. Specifically, (1) the circARID1B promoter is a circARID1B overexpression agent; (2) the circcamap 1 promoter is a circcamap 1 over-expression agent; (3) the circCCNB1 promoter is a circCCNB1 overexpression agent; (4) the circCNN2 promoter is a circCNN2 overexpression agent; (5) the circDHX34 promoter is a circDHX34 overexpression agent; (6) the circEPHB4 promoter is a circEPHB4 overexpression agent; (7) the circEZH2 promoter is a circEZH2 overexpression agent; (8) the circFCHO2 promoter is a circFCHO2 overexpression agent; (9) the circFGFR1 promoter is a circFGFR1 overexpression agent; (10) the circFKBP8 promoter is a circFKBP8 overexpression agent; (11) the circKIAA0368 promoter is a circKIAA0368 overexpression agent; (12) the circMBOAT2 promoter is a circMBOAT2 over-expression agent; (13) the circPIP5K1C promoter is a circPIP5K1C overexpression agent; (14) the circPOLR2A promoter is a circPOLR2A overexpression agent; (15) the circPPP1CB promoter is a circPPP1CB overexpression agent; (16) the circPROSC promoter is a circPROSC overexpression agent; (17) the circPTK2 promoter is a circPTK2 overexpression agent; (18) the circPVT1 promoter is a circPVT1 overexpression agent; (19) the circRELL1 promoter is a circRELL1 overexpression agent; (20) the circSDHAF2 promoter is a circSDHAF2 overexpression agent; (21) the circSLC22a23 promoter is a circSLC22a23 overexpression agent; (22) the circSNHG4 promoter is a circSNHG4 overexpression agent; (23) the circTBCD promoter is a circTBCD overexpression agent; (24) the circTMEM181 promoter is a circTMEM181 overexpression agent; (25) the circUIMC1 promoter is a circUIMC1 overexpression agent; (26) the circVAPB promoter is a circVAPB over-expression agent.

The invention provides application of circular RNA with an incomplete double-chain structure with the length of 16bp-33bp in preparing or screening a systemic lupus erythematosus detection reagent.

In one embodiment, circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp is used as the biomarker.

In one embodiment, the systemic lupus erythematosus detection reagent is used for the judgment and diagnosis of systemic lupus erythematosus.

It should be noted that the detection reagent for systemic lupus erythematosus includes, but is not limited to, liquid form.

In one embodiment, the systemic lupus erythematosus detection reagent is selected from reagents that specifically recognize circular RNAs having incomplete double-stranded structures ranging in length from 16bp to 33 bp. Specifically, the systemic lupus erythematosus detection reagent is selected from (1) a reagent which specifically recognizes circARID 1B; (2) a reagent that specifically recognizes circcamap 1; (3) an agent that specifically recognizes circCCNB 1; (4) a reagent that specifically recognizes circCNN 2; (5) a circDHX34 reagent that specifically recognizes; (6) a reagent that specifically recognizes circEPHB 4; (7) an agent that specifically recognizes circEZH 2; (8) an agent that specifically recognizes circFCHO 2; (9) an agent that specifically recognizes circFGFR 1; (10) a reagent that specifically recognizes circFKBP 8; (11) an agent that specifically recognizes circKIAA 0368; (12) a reagent that specifically recognizes circMBOAT 2; (13) a reagent that specifically recognizes circPIP5K 1C; (14) an agent that specifically recognizes circPOLR 2A; (15) an agent that specifically recognizes circPPP1 CB; (16) an agent that specifically recognizes circPROSC; (17) an agent that specifically recognizes circPTK 2; (18) a reagent that specifically recognizes circPVT 1; (19) a reagent that specifically recognizes circRELL 1; (20) an agent that specifically recognizes circSDHAF 2; (21) an agent that specifically recognizes circSLC22a 23; (22) a reagent that specifically recognizes circSNHG 4; (23) a reagent that specifically recognizes circTBCD; (24) a reagent that specifically recognizes circTMEM 181; (25) one or more of (26) an agent that specifically recognizes circUIMC1 and (26) an agent that specifically recognizes circVAPB.

In one embodiment, the reagent that specifically recognizes the circular RNA having the incomplete double-stranded structure with the length of 16bp to 33bp is a specific detection primer pair of the circular RNA having the incomplete double-stranded structure with the length of 16bp to 33 bp. Specifically, (1) the reagent for specifically recognizing circARID1B is a specific detection primer pair of circARID 1B; (2) the reagent for specifically recognizing circcamasp 1 is a specific detection primer pair of circcamasp 1; (3) the reagent for specifically recognizing the circCCNB1 is a specific detection primer pair of the circCCNB 1; (4) the reagent for specifically recognizing the circCNN2 is a specific detection primer pair of circCNN 2; (5) the circDHX34 reagent for specific recognition is a specific detection primer pair of circDHX 34; (6) the reagent for specifically recognizing the circEPHB4 is a specific detection primer pair of circEPHB 4; (7) the reagent for specifically recognizing the circEZH2 is a specific detection primer pair of the circEZH 2; (8) the reagent for specifically recognizing circFCHO2 is a specific detection primer pair of circFCHO 2; (9) the reagent for specifically recognizing circFGFR1 is a specific detection primer pair of circFGFR 1; (10) the reagent for specifically recognizing the circFKBP8 is a specific detection primer pair of circFKBP 8; (11) the reagent for specifically identifying circKIAA0368 is a specific detection primer pair of circKIAA 0368; (12) the reagent for specifically recognizing circMBOAT2 is a specific detection primer pair of circMBOAT 2; (13) the reagent for specifically recognizing circPIP5K1C is a specific detection primer pair of circPIP5K 1C; (14) the reagent for specifically recognizing the circPOLR2A is a specific detection primer pair of circPOLR 2A; (15) the reagent for specifically recognizing the circPPP1CB is a specific detection primer pair of circPPP1 CB; (16) the reagent for specifically recognizing circPROSC is a specific detection primer pair of circPROSC; (17) the reagent for specifically recognizing the circPTK2 is a specific detection primer pair of circPTK 2; (18) the reagent for specifically recognizing the circPVT1 is a specific detection primer pair of circPVT 1; (19) the reagent for specifically recognizing the circRELL1 is a specific detection primer pair of circRELL 1; (20) the reagent for specifically recognizing circSDHAF2 is a specific detection primer pair of circSDHAF 2; (21) the reagent for specifically recognizing the circSLC22A23 is a specific detection primer pair of the circSLC22A 23; (22) the reagent for specifically recognizing the circSNHG4 is a specific detection primer pair of circSNHG 4; (23) the reagent for specifically recognizing the circTBCD is a specific detection primer pair of the circTBCD; (24) the reagent for specifically recognizing the circTMEM181 is a specific detection primer pair of the circTMEM 181; (25) the reagent for specifically recognizing the circUIMC1 is a specific detection primer pair of circUIMC 1; (26) the reagent for specifically recognizing circVAPB is a specific detection primer pair of circVAPB.

The invention discovers for the first time that the expression quantity of the circular RNA with the incomplete double-chain structure with the length of 16bp-33bp in the peripheral blood mononuclear cells of the systemic lupus erythematosus patient is obviously lower than that of a normal person.

The invention provides application of a reagent for specifically identifying circular RNA with an incomplete double-chain structure with the length of 16bp-33bp in preparation of a systemic lupus erythematosus detection kit.

Specifically, the reagent specifically recognizing the circular RNA having the incomplete double-stranded structure with the length of 16bp-33bp is selected from (1) a reagent specifically recognizing circARID 1B; (2) a reagent that specifically recognizes circcamap 1; (3) an agent that specifically recognizes circCCNB 1; (4) a reagent that specifically recognizes circCNN 2; (5) a circDHX34 reagent that specifically recognizes; (6) a reagent that specifically recognizes circEPHB 4; (7) an agent that specifically recognizes circEZH 2; (8) an agent that specifically recognizes circFCHO 2; (9) an agent that specifically recognizes circFGFR 1; (10) a reagent that specifically recognizes circFKBP 8; (11) an agent that specifically recognizes circKIAA 0368; (12) a reagent that specifically recognizes circMBOAT 2; (13) a reagent that specifically recognizes circPIP5K 1C; (14) an agent that specifically recognizes circPOLR 2A; (15) an agent that specifically recognizes circPPP1 CB; (16) an agent that specifically recognizes circPROSC; (17) an agent that specifically recognizes circPTK 2; (18) a reagent that specifically recognizes circPVT 1; (19) a reagent that specifically recognizes circRELL 1; (20) an agent that specifically recognizes circSDHAF 2; (21) an agent that specifically recognizes circSLC22a 23; (22) a reagent that specifically recognizes circSNHG 4; (23) a reagent that specifically recognizes circTBCD; (24) a reagent that specifically recognizes circTMEM 181; (25) one or more of (26) an agent that specifically recognizes circUIMC1 and (26) an agent that specifically recognizes circVAPB.

Circular RNAs with incomplete double-stranded structure of length 16bp-33bp are used as biomarkers.

In one embodiment, the kit is used for judging and diagnosing systemic lupus erythematosus.

It should be noted that the reagent for specifically recognizing the circular RNA having the incomplete double-stranded structure with the length of 16bp to 33bp includes, but is not limited to, a liquid form.

In one embodiment, the reagent for specifically recognizing the circular RNA having the incomplete double-stranded structure with the length of 16bp-33bp is a specific detection primer pair of the circular RNA having the incomplete double-stranded structure with the length of 16bp-33 bp. Specifically, (1) the reagent for specifically recognizing circARID1B is a specific detection primer pair of circARID 1B; (2) the reagent for specifically recognizing circcamasp 1 is a specific detection primer pair of circcamasp 1; (3) the reagent for specifically recognizing the circCCNB1 is a specific detection primer pair of the circCCNB 1; (4) the reagent for specifically recognizing the circCNN2 is a specific detection primer pair of circCNN 2; (5) the circDHX34 reagent for specific recognition is a specific detection primer pair of circDHX 34; (6) the reagent for specifically recognizing the circEPHB4 is a specific detection primer pair of circEPHB 4; (7) the reagent for specifically recognizing the circEZH2 is a specific detection primer pair of the circEZH 2; (8) the reagent for specifically recognizing circFCHO2 is a specific detection primer pair of circFCHO 2; (9) the reagent for specifically recognizing circFGFR1 is a specific detection primer pair of circFGFR 1; (10) the reagent for specifically recognizing the circFKBP8 is a specific detection primer pair of circFKBP 8; (11) the reagent for specifically identifying circKIAA0368 is a specific detection primer pair of circKIAA 0368; (12) the reagent for specifically recognizing circMBOAT2 is a specific detection primer pair of circMBOAT 2; (13) the reagent for specifically recognizing circPIP5K1C is a specific detection primer pair of circPIP5K 1C; (14) the reagent for specifically recognizing the circPOLR2A is a specific detection primer pair of circPOLR 2A; (15) the reagent for specifically recognizing the circPPP1CB is a specific detection primer pair of circPPP1 CB; (16) the reagent for specifically recognizing circPROSC is a specific detection primer pair of circPROSC; (17) the reagent for specifically recognizing the circPTK2 is a specific detection primer pair of circPTK 2; (18) the reagent for specifically recognizing the circPVT1 is a specific detection primer pair of circPVT 1; (19) the reagent for specifically recognizing the circRELL1 is a specific detection primer pair of circRELL 1; (20) the reagent for specifically recognizing circSDHAF2 is a specific detection primer pair of circSDHAF 2; (21) the reagent for specifically recognizing the circSLC22A23 is a specific detection primer pair of the circSLC22A 23; (22) the reagent for specifically recognizing the circSNHG4 is a specific detection primer pair of circSNHG 4; (23) the reagent for specifically recognizing the circTBCD is a specific detection primer pair of the circTBCD; (24) the reagent for specifically recognizing the circTMEM181 is a specific detection primer pair of the circTMEM 181; (25) the reagent for specifically recognizing the circUIMC1 is a specific detection primer pair of circUIMC 1; (26) the reagent for specifically recognizing circVAPB is a specific detection primer pair of circVAPB.

The kit at least comprises a reagent for specifically recognizing the circular RNA with the incomplete double-chain structure with the length of 16bp-33 bp.

In one embodiment, circular RNA having an incomplete double-stranded structure with a length of 16bp to 33bp is used as the biomarker.

In one embodiment, the kit is used for judging and diagnosing systemic lupus erythematosus.

It should be noted that the reagent for specifically recognizing the circular RNA having the incomplete double-stranded structure with the length of 16bp to 33bp includes, but is not limited to, a liquid form.

In one embodiment, the reagent for specifically recognizing the circular RNA having the incomplete double-stranded structure with the length of 16bp-33bp is a specific detection primer pair of the circular RNA having the incomplete double-stranded structure with the length of 16bp-33 bp. Specifically, (1) the reagent for specifically recognizing circARID1B is a specific detection primer pair of circARID 1B; (2) the reagent for specifically recognizing circcamasp 1 is a specific detection primer pair of circcamasp 1; (3) the reagent for specifically recognizing the circCCNB1 is a specific detection primer pair of the circCCNB 1; (4) the reagent for specifically recognizing the circCNN2 is a specific detection primer pair of circCNN 2; (5) the circDHX34 reagent for specific recognition is a specific detection primer pair of circDHX 34; (6) the reagent for specifically recognizing the circEPHB4 is a specific detection primer pair of circEPHB 4; (7) the reagent for specifically recognizing the circEZH2 is a specific detection primer pair of the circEZH 2; (8) the reagent for specifically recognizing circFCHO2 is a specific detection primer pair of circFCHO 2; (9) the reagent for specifically recognizing circFGFR1 is a specific detection primer pair of circFGFR 1; (10) the reagent for specifically recognizing the circFKBP8 is a specific detection primer pair of circFKBP 8; (11) the reagent for specifically identifying circKIAA0368 is a specific detection primer pair of circKIAA 0368; (12) the reagent for specifically recognizing circMBOAT2 is a specific detection primer pair of circMBOAT 2; (13) the reagent for specifically recognizing circPIP5K1C is a specific detection primer pair of circPIP5K 1C; (14) the reagent for specifically recognizing the circPOLR2A is a specific detection primer pair of circPOLR 2A; (15) the reagent for specifically recognizing the circPPP1CB is a specific detection primer pair of circPPP1 CB; (16) the reagent for specifically recognizing circPROSC is a specific detection primer pair of circPROSC; (17) the reagent for specifically recognizing the circPTK2 is a specific detection primer pair of circPTK 2; (18) the reagent for specifically recognizing the circPVT1 is a specific detection primer pair of circPVT 1; (19) the reagent for specifically recognizing the circRELL1 is a specific detection primer pair of circRELL 1; (20) the reagent for specifically recognizing circSDHAF2 is a specific detection primer pair of circSDHAF 2; (21) the reagent for specifically recognizing the circSLC22A23 is a specific detection primer pair of the circSLC22A 23; (22) the reagent for specifically recognizing the circSNHG4 is a specific detection primer pair of circSNHG 4; (23) the reagent for specifically recognizing the circTBCD is a specific detection primer pair of the circTBCD; (24) the reagent for specifically recognizing the circTMEM181 is a specific detection primer pair of the circTMEM 181; (25) the reagent for specifically recognizing the circUIMC1 is a specific detection primer pair of circUIMC 1; (26) the reagent for specifically recognizing circVAPB is a specific detection primer pair of circVAPB.

The applicant researches and discovers that the overexpression of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp in a model cell human HeLa cell can inhibit the phosphorylation activation of the protein kinase PKR and related protein kinases of a downstream path thereof, however, the overexpression of the circular RNA without the special double-stranded structure, namely circSMARCA5, can not inhibit the phosphorylation activation of the protein kinase PKR and related protein kinases of a downstream path thereof. The ring RNA gene with the incomplete double-chain structure with the length of 16bp-33bp and the expression product thereof are suggested to be a new way for regulating and controlling the phosphorylation activation of the protein PKR involved in the natural immune process and the related protein kinase of the downstream path thereof in the autoimmune diseases.

The applicant researches and discovers that the expression quantity of the circular RNA with the incomplete double-stranded structure with the length of 16bp-33bp in Peripheral Blood Mononuclear Cells (PBMC) of the systemic lupus erythematosus patient is obviously reduced. The ring RNA with the incomplete double-chain structure with the length of 16bp-33bp is over-expressed in the primary cell or the immune cell T cell, so that the phosphorylation activation of the protein kinase PKR and the expression quantity of the cell factor IFN-beta and the systemic lupus erythematosus diagnosis gene can be inhibited. Suggesting that the circular RNA gene with the incomplete double-chain structure with the length of 16bp-33bp and the expression product thereof can become a new way for diagnosing and treating the systemic lupus erythematosus.

The present invention takes circPOLR2A as an example, and describes the characteristics and actions of the circular RNA having a specific structure in the present invention.