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长链非编码RNA(long non-coding RNAs,lncRNAs)是指长度超过200个核苷酸的非编码RNA,多数lncRNAs由RNA聚合酶II参与合成,可具有5’甲基帽和3’PolyA尾,缺乏开放阅读框,不具有蛋白编码能力,在极少数情况下,具有功能的寡肽可转录于某些特定的lncRNAs基因[1-3]。研究发现,lncRNAs参与多种生物学事件,包括生长发育、免疫应答、代谢调控、肿瘤形成等。已有研究表明,lncRNAs可以通过电离辐射诱导表达,并参与细胞对电离辐射的应答反应以及细胞损伤修复过程。对电离辐射相关lncRNAs的研究有助于加深对电离辐射损伤应答机制的认识和了解。本文对lncRNAs的结构功能、调控靶基因方式以及对电离辐射相关lncRNAs的功能和作用方式进行综述。
电离辐射损伤相关长链非编码RNA研究进展
Research advancement on long non-coding RNAs in ionizing radiation-induced damage
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摘要: 长链非编码RNA(lncRNAs)是一类新的功能分子,可通过影响基因转录、蛋白质翻译以及蛋白质稳定性等方式调节下游靶基因,在生长发育、免疫应答、代谢调控以及肿瘤形成等生物学事件中发挥重要作用。已有研究表明lncRNAs可以通过电离辐射诱导表达,并参与细胞对电离辐射的应答反应以及细胞损伤修复过程。通过对电离辐射相关lncRNAs的研究有助于加深对电离辐射损伤应答机制的认识和了解。笔者对lncRNAs的结构功能、调控靶基因方式以及对电离辐射相关lncRNAs的功能和作用方式进行综述。
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关键词:
- 辐射, 电离 /
- RNA, 长链非编码 /
- 损伤应答
Abstract: Long noncoding RNAs (lncRNAs) are emerging functional molecules that can regulate downstream target genes by influencing genetic transcription and protein translation and stability. LncRNAs play an important role in various biological processes, such as growth and development, immune response, metabolic regulation, and oncogenesis. Ionizing radiation can induce the expression of lncRNAs that can participate in ionizing radiation-induced damage response and repair. Thus, studying lncRNAs related to ionizing radiation is helpful in enriching our understanding of the mechanisms of damage response. Herein, we aimed to review the structures, functions, and target gene regulatory mechanisms of lncRNAs in ionizing radiation.-
Key words:
- Radiation, ionizing /
- RNA, long noncoding /
- Damage response
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[1] Mercer TR, Dinger ME, Mattick JS.Long non-coding RNAs:insights into functions[J]. Nat Rev Genet, 2009, 10(3):155-159. DOI:10.1038/nrg2521. [2] Anderson DM, Anderson KM, Chang CL, et al. A micropeptide encoded by a putative long non-coding RNA regulates muscle performance[J]. Cell, 2015, 160(4):595-606. DOI:10.1016/j.cell.2015.01.009. [3] Wilusz JE, Sunwoo H, Spector DL.Long noncoding RNAs:functional surprises from the RNA world[J]. Genes Dev, 2009, 23(13):1494-1504. DOI:10.1101/gad.1800909. [4] Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs[J]. Cell, 2009, 136(4):629-641. DOI:10.1016/j.cell.2009.02.006. [5] Ransohoff JD, Wei Y, Khavari PA. The functions and unique features of long intergenic non-coding RNA[J]. Nat Rev Mol Cell Biol, 2018, 19(3):143-157. DOI:10.1038/nrm.2017.104. [6] Smith MA, Gesell T, Stadler PF, et al. Widespread purifying selection on RNA structure in mammals[J]. Nucleic Acids Res, 2013, 41(17):8220-8236. DOI:10.1093/nar/gkt596. [7] Melissari MT, Grote P. Roles for long non-coding RNAs in physiology and disease[J]. Pflugers Arch, 2016, 468(6):945-958. DOI:10.1007/s00424-016-1804-y. [8] Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals[J]. Nature, 2009, 458(7235):223-227. DOI:10.1038/nature07672. [9] Chen LL, Carmichael GG. Long noncodin g RNAs in mammalian cells:what, where, and why?[J]. Wiley Interdiscip Rev RNA, 2010, 1(1):2-21. DOI:10.1002/wrna.5. [10] Mchugh CA, Chen CK, Chow A, et al. The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3[J].Nature, 2015, 521(7551):232-236. DOI:10.1038/nature14443. [11] Zhou JC, Yang LH, Zhong TY, et al. H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase[J]. Nat Commun, 2015, 6:10221. DOI:10.1038/ncomms 10221. [12] Huang YP, Zheng YF, Jin CY, et al. Long non-coding RNA H19 inhibits adipocyte differentiation of bone marrow mesenchymal stem cells through epigenetic modulation of histone deacetylases[J]. Sci Rep, 2016, 628(6):28897. DOI:10.1038/srep28897. [13] Morris KV, Sharon S, Turner AM, et al. Bidirectional transcription directs both transcriptional gene activation and suppression in human cells[J/OL]. PLoS Genet, 2008, 4(11): e1000258[2018-01-20].http://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000258&type=printable. DOI: 10.1371/journal.pgen.1000258. [14] Martens JA, Laprade L, Winston F. Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene[J]. Nature, 2004, 429(6991):571-574. DOI:10.1038/nature02538. [15] Tripathi V, Ellis JD, Shen Z, et al.The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation[J]. Mol Cell, 2010, 39(6):925-938.DOI:10.1016/j.molcel.2010.08.011. [16] Hirose T, Virnicchi G, Tanigawa A, et al. NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies[J]. Mol Biol Cell, 2014, 25(1):169-183. DOI:10.1091/mbc.E13-09-0558. [17] Angrand PO, Vennin C, Le Bourhis XL. The role of long non-coding RNAs in genome formatting and expression[J]. Front Genet, 2015, 429(6):165. DOI:10.3389/fgene.2015.00165. [18] Deckbar D, Jeggo PA, Löbrich M.Understanding the limitations of radiation-induced cell cycle checkpoints[J]. Crit Rev Biochem Mol Biol, 2011, 46(4):271-283. DOI:10.3109/10409238. 2011.575764. [19] Warmerdam DO, Kanaar R. Dealing with DNA damage:Relationships between checkpoint and repair pathways[J]. Mutat Res, 2010, 704(1/3):2-11. DOI:10.1016/j.mrrev.2009.12.001. [20] Liu X, Li D, Zhang W, et al. Long non-coding RNA gadd7 interacts with TDP-43 and regulates Cdk6 mRNA decay[J]. EMBO J, 2012, 31(23):4415-4427. DOI:10.1038/emboj.2012.292. [21] Wang X, Arai S, Song X, et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription[J]. Nature, 2008, 454(720):126-130. DOI:10.1038/nature06992. [22] Zhang M, Gao C, Yang Y, et al. Long noncoding RNA CRNDE/PRC2 participated in the radiotherapy resistance of human lung adenocarcinoma through targeting p21 expression[J]. Oncol Res, 2017. DOI:10.3727/096504017X14944585873668. [23] Jiang Y, Li Y, Fang S, et al. The role of MALAT1 correlates with HPV in cervical cancer[J]. Oncol Lett, 2014, 7(6):2135-2141. DOI:10.3892/ol.2014.1996. [24] Wang J, Su L, Chen X, et al. MALAT1 promotes cell proliferation in gastric cancer by recruiting SF2/ASF[J]. Biomed Pharmacother, 2014, 68(5):557-564. DOI:10.1016/j.biopha.2014.04.007. [25] Lu H, He Y, Lin L, et al.Long non-coding RNA MALAT1 modulates radiosensitivity of HR-HPV+ cervical cancer via sponging miR-145[J]. Tumour Biol, 2016, 37(2):1683-1691. DOI:10.1007/s13277-015-3946-5. [26] Prensner JR, Chen W, Iyer MK, et al. PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer[J]. Cancer Res, 2014, 74(6):1651-1660. DOI:10.1158/0008-5472. CAN-13-3159. [27] Zhang Y, He Q, Hu Z, et al. Long noncoding RNA LINP1 regulates double strand DNA break repair in triple negative breast cancer[J].Nat Struct Mol Biol, 2016, 23(6):522-530. DOI:10.1038/nsmb.3211. [28] Sharma V, Khurana S, Kubben N, et al. A BRCA1-interacting lncRNA regulates homologous recombination[J]. EMBO Rep, 2015, 16(11):1520-1534. DOI:10.15252/embr.201540437. [29] Wan G, Hu X, Liu Y, et al. A novel non-coding RNA lncRNA-JADE connects DNA damage signalling to histone H4 acetylation[J]. EMBO J, 2013, 32(21):2833-2847. DOI:10.1038/emboj.2013.221. [30] Wang G, Li Z, Zhao Q, et al. LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/β-catenin signaling pathway[J]. Oncol Rep, 2014, 31(4):1839-1845. DOI:10.3892/or.2014.3047. [31] Shen Y, Liu Y, Sun T, et al. LincRNA-p21 knockdown enhances radiosensitivity of hypoxic tumor cells by reducing autophagy through HIF-1/Akt/mTOR/P70S6K pathway[J]. Exp Cell Res, 2017, 358(2):188-198. DOI:10.1016/j.yexcr.2017.06.016. [32] Wan GH, Mathur R, Hu XX, et al. Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway[J].Cell Signal, 2013, 25(5):1086-1095. DOI:10.1016/j.cellsig.2013. 02.006. [33] Hu XG, Jiang HJ, Jiang XJ. Downregulation of lncRNA ANRIL inhibits proliferation, induces apoptosis, and enhances radiosensitivity in nasopharyngeal carcinoma cells through regulating miR-125a[J]. Cancer Biol Ther, 2017, 18(5):331-338.DOI:10.1080/15384047.2017.1310348. [34] Hung T, Wang Y, Lin MF, et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters[J]. Nat Genet, 2011, 43(7):621-629. DOI:10.1038/ng.848. [35] O'leary VB, Ovsepian SV, Carrascosa LG, et al. PARTICLE, a triplex-forming long ncRNA, regulates locus-specific methylation in response to low-dose irradiation[J]. Cell Rep, 2015, 11(3):474-485. DOI:10.1016/j.celrep.2015.03.043. [36] Tan JM, Qiu KF, Li MY, et al. Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells[J]. FEBS Lett, 2015, 589(20 Pt B):3175-3181.DOI:10.1016/j.febslet.2015.08.020.
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