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环状RNA(circRNA)作为一类非编码RNA(ncRNA),具备一些生物特性,包括特殊的圆环结构、较长的半衰期、相对保守性及较好的稳定性等。circRNA在各种疾病中的重要调控作用。并且circRNA可通过竞争性内源RNA(ceRNA)机制,转录调控外泌体携带等调控肿瘤进展。在此,本文阐述了circRNA的几种环化理论和相关出核机制,以及circRNA在肿瘤中顺利出核后,如何在胞质及胞外发挥其生物学功能。circRNA在多种肿瘤都可作为一个有前景的标志物。因此对circRNA出核机制及核外生物学功能的深入研究将为临床上的肿瘤治疗提供新线索。
Abstract：AS a class of non-coding RNAs(ncRNA), circular RNAs(circRNAs) can show some biological properties, including special circular structure, prolonged half-life, relatively conservative and better stability, etc. It has been verified that circRNA are essential to regulating various diseases. In addition, circRNA involved in tumorigenesis through competing endogenous RNAs(ceRNA) mechanism, transcriptional regulation and exosome-based delivery and so on. There, this paper elaborates several cyclization theories and correlated nuclear export mechanism. And, how do circRNA construe its biological function after are exported from the nucleus. Besides, circRNA are considered to be biomarkers for multiple tumors. In-depth study of circRNA export from nucleus and its biological function outside the nucleus will provide new clues for clinical management of tumors.
[1] ENUKA Y,LAURIOLA M,FELDMAN M,et al.Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor [J].Nucleic Acids Res,2016,44(3):1370-1383.
[2] DONG R,MA X,CHEN L,et al.Increased complexity of circRNA expression during species evolution [J].RNA Biol,2017,14(8):1064-1074.
[3] JECK W,SORRENTINO J,WANG K,et al.Circular RNAs are abundant,conserved,and associated with ALU repeats [J].RNA,2013,19(2):141-157.
[4] CONN S J,PILLMAN K A,TOUBIA J,et al.The RNA binding protein quaking regulates formation of circRNAs [J].Cell,2015,160(6):1125-1134.
[5] ASHWAL-FLUSS R,MEYER M,PAMUDURTI N,et al.circRNA biogenesis competes with pre-mRNA splicing [J].Mol Cell,2014,56(1):55-66.
[6] BAZAK L,LEVANON E,EISENBERG E.Genome-wide analysis of Alu editability [J].Nucleic Acids Res,2014,42(11):6876-6884.
[7] WILUSZ J E.Circular RNAs:Unexpected outputs of many protein-coding genes [J].RNA Biol,2017,14(8):1007-1017.
[8] HUANG C,LIANG D,TATOMER D C,et al.A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs [J].Genes Dev,2018,32(9-10):639-644.
[9] CUI X,WANG J,GUO Z,et al.Emerging function and potential diagnostic value of circular RNAs in cancer [J].Mol Cancer,2018,17(1):123.
[10] YAMAZAKI T,FUJIWARA N,YUKINAGA H,et al.The closely related RNA helicases,UAP56 and URH49,preferentially form distinct mRNA export machineries and coordinately regulate mitotic progression [J].Mol Biol Cell,2010,21(16):2953-2965.
[11] CHEN R X,CHEN X,XIA L P,et al.N(6)-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis [J].Nat Commun,2019,10(1):4695.
[12] YANG Y,FAN X,MAO M,et al.Extensive translation of circular RNAs driven by N-methyladenosine [J].Cell Res,2017,27(5):626-641.
[13] ZHANG J,ZHANG X L,LI C D,et al.Circular RNA profiling provides insights into their subcellular distribution and molecular characteristics in HepG2 cells[J].RNA Biol,2019,16(2):220-232.
[14] LI Y,ZHENG Q P,BAO C Y,et al.Circular RNA is enriched and stable in exosomes:a promising biomarker for cancer diagnosis [J].Cell Res,2015,25(8):981-984.
[15] SONG X,LIANG Y,SANG Y,et al.circHMCU promotes proliferation and metastasis of breast cancer by sponging the let-7 family [J/OL].Mol Ther Nucleic Acids,2020,20:e518-e533.2020-06-05 [2020-09-10].https://pubmed.ncbi.nlm.nih.gov/32330870/.
[16] LI W,YANG F Q,SUN C M,et al.circPRRC2A promotes angioge-nesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma [J].Theranostics,2020,10(10):4395-409.
[17] OU R,MO L,TANG H,et al.CircRNA-AKT1 sequesters miR-942-5p to upregulate AKT1 and promote cervical cancer progre-ssion [J/OL].Mol Ther Nucleic Acids,2020,20:e308-e322.2020-06-05 [2020-09-10].https://pubmed.ncbi.nlm.nih.gov/32193155/.
[18] DING C,YI X,WU X,et al.Exosome-mediated transfer of circRNA CircNFIX enhances temozolomide resistance in glioma [J/OL].Cancer Lett,2020,479:e1-e12.2020-06-01 [2020-08-22].https://pubmed.ncbi.nlm.nih.gov/32194140/.
[19] YANG Q,DU W W,WU N,et al.A circular RNA promotes tumorigenesis by inducing c-myc nuclear translocation [J].Cell Death Differ,2017,24(9):1609-1620.
[20] WONG C H,LOU U K,LI Y,et al.CircFOXK2 promotes growth and metastasis of pancreatic ductal adenocarcinoma by complexing with RNA-binding proteins and sponging MiR-942 [J].Cancer Res,2020,80(11):2138-2149.
[21] PAN Z,CAI J,LIN J,et al.A novel protein encoded by circFNDC3B inhibits tumor progression and EMT through regulating Snail in colon cancer [J].Mol Cancer,2020,19(1):71.
[22] JIE M,WU Y,GAO M,et al.CircMRPS35 suppresses gastric cancer progression via recruiting KAT7 to govern histone modification [J].Mol Cancer,2020,19(1):56.
[23] LI J,LI Z,JIANG P,et al.Circular RNA IARS (circ-IARS) secreted by pancreatic cancer cells and located within exosomes regulates endothelial monolayer permeability to promote tumor metastasis [J].J Exp Clin Cancer Res,2018,37(1):177.
[24] HUANG X Y,HUANG Z L,HUANG J,et al.Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis [J].J Exp Clin Cancer Res,2020,39(1):20.
[25] WANG S,HU Y,LV X,et al.Circ-0000284 arouses malignant phenotype of cholangiocarcinoma cells and regulates the biological functions of peripheral cells through cellular communication [J].Clin Sci,2019,133(18):1935-53.
[26] OU Z L,LUO Z,WEI W,et al.Hypoxia-induced shedding of MICA and HIF1A-mediated immune escape of pancreatic cancer cells from NK cells:role of circ_0000977/miR-153 axis [J].RNA Biol,2019,16(11):1592-1603.
[27] AMARAL P,DINGER M,MERCER T,et al.The eukaryotic genome as an RNA machine [J].Science,2008,319(5871):1787-1789.
[28] SALMENA L,POLISENO L,TAY Y,et al.A ceRNA hypothesis:the Rosetta Stone of a hidden RNA language?[J].Cell,2011,146(3):353-358.
[29] SANGER H,KLOTZ G,RIESNER D,et al.Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures [J].Proceed Nat Academy Sci United States Am,1976,73(11):3852-3856.
[30] HSU M,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.
[31] 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.
[32] 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.
基本信息:
DOI：10.13699/j.cnki.1001-6821.2021.07.032
中图分类号:R730.2
引用信息:
[1]谭芳,胡娟,张鑫鑫等.环状RNA的出核机制及在肿瘤中作用的研究现状[J].中国临床药理学杂志,2021,37(07):918-921+933.DOI:10.13699/j.cnki.1001-6821.2021.07.032.
基金信息:
湖南省自然科学青年基金资助项目(2018JJ3454;2019JJ50500); 湖南省大学生创新训练基金资助项目(2315); 衡阳市科技计划基金资助项目(2017KJ286)