CircRNA在自身免疫疾病中的研究进展
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摘要
Circular RNA(简称CircRNA)为一类新发现、长链非编码的内源性环状RNA分子,能够参与基因组转录及转录后水平的调节,竞争内源性RNA特异性结合miRNA,进而通过调控其活性影响下游靶基因的表达,参与发育、凋亡,影响诸多疾病的进程。最新的研究证实,CircRNA调控了类风湿性关节炎(rheumatoid arthritis,RA)、系统性红斑狼疮(systemic lupus erythematosus,SLE)、多发性硬化症(multiple sclerosis,MS)等自身免疫性疾病的发生,有望作为此类疾病诊断标志物或治疗靶标。本文就CircRNA的生物学特性及其在自身免疫性疾病中的研究状况作一综述。
Circular RNA(CircRNA)is a newly discovered,long chain and noncoding endogenous circular RNA molecule,which participates in the regulation of transcriptional and post transcriptional levels of genome and competes for endogenous RNA to bind miRNA specifically thus involves in the development,apoptosis and many diseases by regulating the expression of miRNA downstream target gene. The latest research has confirmed that CircRNA regulates the occurrence of autoimmune diseases such as rheumatoid arthritis(RA) systemic lupus erythematosus(SLE) and multiple sclerosis(MS),and is expected to be a diagnostic marker or therapeutic target for such diseases. This article reviews the current biological characteristics of CircRNA and progress in research on its role in autoimmune diseases.
Circular RNA(CircRNA)is a newly discovered,long chain and noncoding endogenous circular RNA molecule,which participates in the regulation of transcriptional and post transcriptional levels of genome and competes for endogenous RNA to bind miRNA specifically thus involves in the development,apoptosis and many diseases by regulating the expression of miRNA downstream target gene. The latest research has confirmed that CircRNA regulates the occurrence of autoimmune diseases such as rheumatoid arthritis(RA) systemic lupus erythematosus(SLE) and multiple sclerosis(MS),and is expected to be a diagnostic marker or therapeutic target for such diseases. This article reviews the current biological characteristics of CircRNA and progress in research on its role in autoimmune diseases.
引文
[1]GUO J U,AGARWAL V,GUO H,et al.Expanded identification and characterization of mammalian circular RNAs[J].Genome Biol,2014,15(7):409.
[2]SANGER H L,KLOTZ G,RIESNER D,et al.Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures[J].Proc Natl Acad Sci USA,1976,73(11):3852-3856.
[3]HSU M T,COCA-PRADOS M.Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells[J].Nature,1979,280(5720):339-340.
[4]MATSUMODTO Y,FISHEL R,WICKNER R B.Circular single-stranded RNA replicon in Saccharomyces cerevisiae[J].Proc Natl Acad Sci USA,1990,87(19):7628-7632.
[5]NIGRO J M,CHO K R,FEARON E R,et al.Scrambled exons[J].Cell,1991,64(3):607-613.
[6]MEMCZAK S,JENS M,ELEFSINIOTI A,et al.Circular RNAs are a large class of animal RNAs with regulatory potency[J].Nature,2013,495(7441):333-338.
[7]LI Y,ZHENG Q,BAO C,et al.Circular RNA is enriched and stable in exosomes:a promising biomarker for cancer diagnosis[J].Cell Res,2015,25(8):981-984.
[8]GREENE J,BAIRD A M,BRADY L,et al.Circular RNAs:biogenesis,function and role in human diseases[J].Front Mol Biosci,2017,4:38.
[9]SUZUKI H,ZUO Y,WANG J,et al.Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing[J].Nucleic Acids Res,2006,34(8):e63.
[10]HANSEN T B,JENSEN T I,CLAUSEN B H,et al.Natural RNA circles function as efficient microRNA sponges[J].Nature,2013,495(7441):384-388.
[11]ASHWAL-FLUSS R,MEYER M,PAMUDURTI N R,et al.circRNA biogenesis competes with pre-mRNA splicing[J].Mol Cell,2014,56(1):55-66.
[12]CHAO C W,CHAN D C,KUO A,et al.The mouse formin(Fmn)gene:abundant circular RNA transcripts and gene-targeted deletion analysis[J].Mol Med,1998,4(9):614-628.
[13]YANG Y,GAO X,ZHANG M,et al.Novel role of FBXW7circular RNA in repressing glioma tumorigenesis[J].J Natl Cancer Inst,2018,110(3):[14]HONG B K,YOU S,YOO S A,et al.MicroRNA-143 and-145modulate the phenotype of synovial fibroblasts in rheumatoid arthritis[J].Exp Mol Med,2017,49(8):e363.
[15]WU G C,PAN H F,LENG R X,et al.Emerging role of long noncoding RNAs in autoimmune diseases[J].Autoimmun Rev,2015,14(9):798-805.
[16]ZHANG Y,LIU H,LI W,et al.CircRNA_100269 is downregulated in gastric cancer and suppresses tumor cell growth by targeting miR-630[J].Aging(Albany NY),2017,9(6):1585-1594.
[17]WAN L,ZHANG L,FAN K,et al.Circular RNA-ITCH suppresses lung cancer proliferation via inhibiting the Wnt/betacatenin pathway[J].Biomed Res Int,2016,2016:1579490.
[18]MURATA K,FURU M,YOSHITOMI H,et al.Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis[J].PLoS One,2013,8(7):e69118.
[19]CHEN S Y,HSU W T,CHEN Y L,et al.Lymphocyte-activation gene 3(+)(LAG3(+))forkhead box protein 3(-)(FOX-P3(-))regulatory T cells induced by B cells alleviates joint inflammation in collagen-induced arthritis[J].J Autoimmun,2016,68:75-85.
[20]JIN L,YI J,GAO Y,et al.MiR-630 inhibits invasion and metastasis in esophageal squamous cell carcinoma[J].Acta Biochim Biophys Sin(Shanghai),2016,48(9):810-819.
[21]OUYANG Q,WU J,JIANG Z,et al.Microarray expression profile of circular RNAs in peripheral blood mononuclear cells from rheumatoid arthritis patients[J].Cell Physiol Biochem,2017,42(2):651-659.
[22]ZHENG F,YU X,HUANG J,et al.Circular RNA expression profiles of peripheral blood mononuclear cells in rheumatoid arthritis patients,based on microarray chip technology[J].Mol Med Rep,2017.
[23]PAULEY K M,SATOH M,CHAN A L,et al.Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients[J].Arthritis Res Ther,2008,10(4):R101.
[24]CUI Y,SHENG Y,ZHANG X.Genetic susceptibility to SLE:recent progress from GWAS[J].J Autoimmun,2013,41:25-33.
[25]LIU Y,DONG J,MU R,et al.MicroRNA-30a promotes B cell hyperactivity in patients with systemic lupus erythematosus by direct interaction with Lyn[J].Arthritis Rheum,2013,65(6):1603-1611.
[26]ZHAO S,WANG Y,LIANG Y,et al.MicroRNA-126 regulates DNA methylation in CD4+T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1[J].Arthritis Rheum,2011,63(5):1376-1386.
[27]TANG Y,LUO X,CUI H,et al.MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins[J].Arthritis Rheum,2009,60(4):1065-1075.
[28]LENG R X,HUANG A F,JIA H,et al.Role of microRNA-155 in autoimmunity[J].Cytokine Growth Factor Rev,2011,22(3):141-147.
[29]XU H,GUO S,LI W,et al.The circular RNA Cdr1as,via miR-7 and its targets,regulates insulin transcription and secretion in islet cells[J].Sci Rep,2015,5:12453.
[30]SEN R,GHOSAL S,DAS S,et al.Competing endogenous RNA:the key to posttranscriptional regulation[J].Sci World J,2014,2014:896206.
[31]LI Z,HUANG C,BAO C,et al.Exon-intron circular RNAs regulate transcription in the nucleus[J].Nat Struct Mol Biol,2015,22(3):256-264.
[32]LI H,LI K,LAI W,et al.Comprehensive circular RNA profiles in plasma reveals that circular RNAs can be used as novel biomarkers for systemic lupus erythematosus[J].Clin Chim Acta,2018.
[33]NOSEWORTHY J H,LUCCHINETTI C,RODRIGUEZ M,et al.Multiple sclerosis[J].N Engl J Med,2000,343(13):938-952.
[34]RACOSTA J M,KIMPINSKI K,MORROW S A,et al.Autonomic dysfunction in multiple sclerosis[J].Auton Neurosci,2015,193:1-6.
[35]EHYA F,ABDUL TEHRANI H,GARSHASBI M,et al.Identification of miR-24 and miR-137 as novel candidate multiple sclerosis miRNA biomarkers using multi-staged data analysis protocol[J].Mol Biol Res Commun,2017,6(3):127-140.
[36]ZHANG F,GAO C,MA X F,et al.Expression profile of long noncoding RNAs in peripheral blood mononuclear cells from multiple sclerosis patients[J].CNS Neurosci Ther,2016,22(4):298-305.
[37]IPARRAGUIRRE L,MU譙OZ-CULLA M,PRADA-LUENGO I,et al.Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis[J].Hum Mol Genet,2017,26(18):3564-3572.
[38]MOORE C S,RAO V T,DURAFOURT B A,et al.miR-155as a multiple sclerosis-relevant regulator of myeloid cell polarization[J].Ann Neurol,2013,74(5):709-720.
[2]SANGER H L,KLOTZ G,RIESNER D,et al.Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures[J].Proc Natl Acad Sci USA,1976,73(11):3852-3856.
[3]HSU M T,COCA-PRADOS M.Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells[J].Nature,1979,280(5720):339-340.
[4]MATSUMODTO Y,FISHEL R,WICKNER R B.Circular single-stranded RNA replicon in Saccharomyces cerevisiae[J].Proc Natl Acad Sci USA,1990,87(19):7628-7632.
[5]NIGRO J M,CHO K R,FEARON E R,et al.Scrambled exons[J].Cell,1991,64(3):607-613.
[6]MEMCZAK S,JENS M,ELEFSINIOTI A,et al.Circular RNAs are a large class of animal RNAs with regulatory potency[J].Nature,2013,495(7441):333-338.
[7]LI Y,ZHENG Q,BAO C,et al.Circular RNA is enriched and stable in exosomes:a promising biomarker for cancer diagnosis[J].Cell Res,2015,25(8):981-984.
[8]GREENE J,BAIRD A M,BRADY L,et al.Circular RNAs:biogenesis,function and role in human diseases[J].Front Mol Biosci,2017,4:38.
[9]SUZUKI H,ZUO Y,WANG J,et al.Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing[J].Nucleic Acids Res,2006,34(8):e63.
[10]HANSEN T B,JENSEN T I,CLAUSEN B H,et al.Natural RNA circles function as efficient microRNA sponges[J].Nature,2013,495(7441):384-388.
[11]ASHWAL-FLUSS R,MEYER M,PAMUDURTI N R,et al.circRNA biogenesis competes with pre-mRNA splicing[J].Mol Cell,2014,56(1):55-66.
[12]CHAO C W,CHAN D C,KUO A,et al.The mouse formin(Fmn)gene:abundant circular RNA transcripts and gene-targeted deletion analysis[J].Mol Med,1998,4(9):614-628.
[13]YANG Y,GAO X,ZHANG M,et al.Novel role of FBXW7circular RNA in repressing glioma tumorigenesis[J].J Natl Cancer Inst,2018,110(3):[14]HONG B K,YOU S,YOO S A,et al.MicroRNA-143 and-145modulate the phenotype of synovial fibroblasts in rheumatoid arthritis[J].Exp Mol Med,2017,49(8):e363.
[15]WU G C,PAN H F,LENG R X,et al.Emerging role of long noncoding RNAs in autoimmune diseases[J].Autoimmun Rev,2015,14(9):798-805.
[16]ZHANG Y,LIU H,LI W,et al.CircRNA_100269 is downregulated in gastric cancer and suppresses tumor cell growth by targeting miR-630[J].Aging(Albany NY),2017,9(6):1585-1594.
[17]WAN L,ZHANG L,FAN K,et al.Circular RNA-ITCH suppresses lung cancer proliferation via inhibiting the Wnt/betacatenin pathway[J].Biomed Res Int,2016,2016:1579490.
[18]MURATA K,FURU M,YOSHITOMI H,et al.Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis[J].PLoS One,2013,8(7):e69118.
[19]CHEN S Y,HSU W T,CHEN Y L,et al.Lymphocyte-activation gene 3(+)(LAG3(+))forkhead box protein 3(-)(FOX-P3(-))regulatory T cells induced by B cells alleviates joint inflammation in collagen-induced arthritis[J].J Autoimmun,2016,68:75-85.
[20]JIN L,YI J,GAO Y,et al.MiR-630 inhibits invasion and metastasis in esophageal squamous cell carcinoma[J].Acta Biochim Biophys Sin(Shanghai),2016,48(9):810-819.
[21]OUYANG Q,WU J,JIANG Z,et al.Microarray expression profile of circular RNAs in peripheral blood mononuclear cells from rheumatoid arthritis patients[J].Cell Physiol Biochem,2017,42(2):651-659.
[22]ZHENG F,YU X,HUANG J,et al.Circular RNA expression profiles of peripheral blood mononuclear cells in rheumatoid arthritis patients,based on microarray chip technology[J].Mol Med Rep,2017.
[23]PAULEY K M,SATOH M,CHAN A L,et al.Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients[J].Arthritis Res Ther,2008,10(4):R101.
[24]CUI Y,SHENG Y,ZHANG X.Genetic susceptibility to SLE:recent progress from GWAS[J].J Autoimmun,2013,41:25-33.
[25]LIU Y,DONG J,MU R,et al.MicroRNA-30a promotes B cell hyperactivity in patients with systemic lupus erythematosus by direct interaction with Lyn[J].Arthritis Rheum,2013,65(6):1603-1611.
[26]ZHAO S,WANG Y,LIANG Y,et al.MicroRNA-126 regulates DNA methylation in CD4+T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1[J].Arthritis Rheum,2011,63(5):1376-1386.
[27]TANG Y,LUO X,CUI H,et al.MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins[J].Arthritis Rheum,2009,60(4):1065-1075.
[28]LENG R X,HUANG A F,JIA H,et al.Role of microRNA-155 in autoimmunity[J].Cytokine Growth Factor Rev,2011,22(3):141-147.
[29]XU H,GUO S,LI W,et al.The circular RNA Cdr1as,via miR-7 and its targets,regulates insulin transcription and secretion in islet cells[J].Sci Rep,2015,5:12453.
[30]SEN R,GHOSAL S,DAS S,et al.Competing endogenous RNA:the key to posttranscriptional regulation[J].Sci World J,2014,2014:896206.
[31]LI Z,HUANG C,BAO C,et al.Exon-intron circular RNAs regulate transcription in the nucleus[J].Nat Struct Mol Biol,2015,22(3):256-264.
[32]LI H,LI K,LAI W,et al.Comprehensive circular RNA profiles in plasma reveals that circular RNAs can be used as novel biomarkers for systemic lupus erythematosus[J].Clin Chim Acta,2018.
[33]NOSEWORTHY J H,LUCCHINETTI C,RODRIGUEZ M,et al.Multiple sclerosis[J].N Engl J Med,2000,343(13):938-952.
[34]RACOSTA J M,KIMPINSKI K,MORROW S A,et al.Autonomic dysfunction in multiple sclerosis[J].Auton Neurosci,2015,193:1-6.
[35]EHYA F,ABDUL TEHRANI H,GARSHASBI M,et al.Identification of miR-24 and miR-137 as novel candidate multiple sclerosis miRNA biomarkers using multi-staged data analysis protocol[J].Mol Biol Res Commun,2017,6(3):127-140.
[36]ZHANG F,GAO C,MA X F,et al.Expression profile of long noncoding RNAs in peripheral blood mononuclear cells from multiple sclerosis patients[J].CNS Neurosci Ther,2016,22(4):298-305.
[37]IPARRAGUIRRE L,MU譙OZ-CULLA M,PRADA-LUENGO I,et al.Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis[J].Hum Mol Genet,2017,26(18):3564-3572.
[38]MOORE C S,RAO V T,DURAFOURT B A,et al.miR-155as a multiple sclerosis-relevant regulator of myeloid cell polarization[J].Ann Neurol,2013,74(5):709-720.