心脏重构与再生专刊

非编码RNA调控心脏重构与再生

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  • 1. 浙江大学医学院附属第二医院浙江省心血管病诊治重点实验室, 杭州310009;
    2. 浙江大学转化医学研究院, 杭州310029
陈静海(1978—), 男, 研究员, 博士生导师, 博士, 研究方向为非编码核酸调控心血管疾病与再生. E-mail: Jinghaichen@zju.edu.cn

收稿日期: 2016-04-22

  网络出版日期: 2016-06-30

基金资助

国家自然科学基金资助项目(81470382)

Non-coding RNAs mediate cardiac remodeling and regeneration

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  • 1. Provincial Key Laboratory of Cardiovascular Research, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China;
    2. Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China

Received date: 2016-04-22

  Online published: 2016-06-30

摘要

近年来, 越来越多的证据表明, 大量的非编码RNA(non-coding RNAs, ncRNAs)在基因的表达调控、细胞和机体的生理功能维持与病理环境调节方面都有重要作用, 其中主要包括微小RNA(microRNAs, miRNAs) 和长链非编码RNA(long non-coding RNAs, lncRNAs).心脏重构与再生是心血管疾病领域的关键问题, 其调控过程非常复杂, 包括表观遗传、转录、转录后及翻译水平的调控. 大量研究发现在转录后水平, miRNAs 通过负性调节靶标的表达调控心脏发育、疾病及再生进程. 近期研究揭示, lncRNAs 在心脏发育和疾病中具有潜在的作用, 可通过表观遗传、转录及转录后水平发挥作用. lncRNAs 已成为继miRNAs 之后的又一重要的调节性非编码RNA. 就非编码RNA 在心脏重构及再生进程中的调控作用进行综述.

本文引用格式

高峰1,2, 陈静海1,2 . 非编码RNA调控心脏重构与再生[J]. 上海大学学报(自然科学版), 2016 , 22(3) : 302 -309 . DOI: 10.3969/j.issn.1007-2861.2016.03.021

Abstract

Recently, more and more evidences indicate that a large number of non-coding RNAs (ncRNAs) are involved in gene expression, physiological and pathological regulation, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Cardiac remodeling and regeneration are key to cardiovascular biology and diseases. Regulation of gene expression during cardiac remodeling and regeneration is complicated, involving epigenetic, transcriptional, post-transcriptional and translational regulation. In the past decade, miRNAs have drawn much attention for their impact on cardiovascular diseases and regeneration. miRNAs negatively regulate the expression of the target genes through post-transcriptional regulation. Recent research uncovered that lncRNAs play an important role in cardiac development and diseases, involving epigenetic, transcriptional and post-transcriptional regulation, making lncRNAs become another group of key regulatory non-coding RNAs. This paper summarizes the recent progress in the study of non-coding RNAs in cardiac remodeling and cardiac regeneration.

参考文献

[1] Dunham I, Kundaje A, Aldred S F, et al. An integrated encyclopedia of DNA elements in the human genome [J]. Nature, 2012, 489(7414): 57-74.
[2] Lee Y, Ahn C, Han J, et al. The nuclear RNase Ⅲ Drosha initiates microRNA processing [J]. Nature, 2003, 425(6956): 415-419.
[3] Lee Y, Jeon K, Lee J T, et al. MicroRNA maturation: stepwise processing and subcellular localization [J]. EMBO J, 2002, 21(17): 4663-4670.
[4] Khvorova A, Reynolds A, Jayasena S D. Functional siRNAs and miRNA exhibit strand bias [J]. Cell, 2003, 115(2): 209-216.
[5] Zhao Y, Ransom J F, Li A, et al. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2 [J]. Cell, 2007, 129(2): 303-317.
[6] Chen J F, Murchison E P, Tang R, et al. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure [J]. Proc Natl Acad Sci USA, 2008, 105(6): 2111-2116.
[7] Rao P K, Toyama Y, Chiang H R, et al. Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure [J]. Circ Res, 2009, 105(6): 585-594.
[8] Ding J, Chen J, Wang Y, et al. Trbp regulates heart function through microRNA-mediated Sox6 repression [J]. Nature Genetics, 2015, DOI: 10.1038/ng.3324.
[9] Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific micro-RNA that targets Hand2 during cardiogenesis [J]. Nature, 2005, 436(7048): 214-220.

[10] Liu N, Bezprozvannaya S, Williams W, et al. MicroRNA-133a regulates cardiomyocyte proliferation and suppresses smoothmuscle gene expression in the heart [J]. Genes Dev, 2008, 22(23): 3242-3254.
[11] Van R E, Sutherland L B, Liu N, et al. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure [J]. Proc Natl Acad Sci USA, 2006, 103(48): 18255-18260.
[12] Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts [J]. Nature, 2008, 456(7224): 980-984.
[13] Patrick D M, Montgomery R L, Qi X, et al. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice [J]. J Clin Invest, 2010, 120(11): 3912-3916.
[14] Lin Z, Murtaza I, Wang K, et al. miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy [J]. Proc Natl Acad Sci USA, 2009, 106(10): 12103-12108.
[15] Dong Z, Ma J, Yu Y, et al. Silencing of miR-195 reduces diabetic cardiomyopathy in mice [J]. Diabetologia, 2015, 58(8): 1949-1958.
[16] Huang Z P, Chen J, Seok H Y, et al. MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress [J]. Circ Res, 2013, 112(5): 1234-1243.
[17] Hee Y S, Chen J, Masaharu K, et al. Loss of microRNA-155 protects the heart from pathological cardiac hypertrophy [J]. Circ Res, 2014, 114(10): 1585-1595.
[18] Van R E, Quiat D, Johnson B A, et al. A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance [J]. Dev Cell, 2009, 17(5): 662-673.
[19] Callis T E, Pandya K, Seok H Y, et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice [J]. J Clin Invest, 2009, 119(9): 2772-2786.
[20] Van R E, Sutherland L B, Qi X, et al. Control of stress-dependent cardiac growth and gene expression by a microRNA [J]. Science, 2007, 316(5824): 575-579.
[21] Duisters R F, Tijsen A J, Schroen B, et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocarolial matrix remodeling [J]. Circ Res, 2009, 104(2): 170-178.
[22] Van R E, Sutherland L B, Thatcher J E, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis [J]. Proc Natl Acad Sci USA, 2008, 105: 13027-13032.
[23] Bergmann O, Bhardwaj R D, Bernard S, et al. Evidence for cardiomyocyte renewal in humans [J]. Science, 2009, 324: 98-102.
[24] Porrello E R, Mahmoud A I, Simpson E, et al. Transient regenerative potential of the neonatal mouse heart [J]. Science, 2011, 331: 1078-1080.
[25] Porrello E R, Johnson B A, Aurora A B, et al. miR-15 family regulates postnatal mitotic arrest of cardiomyocytes [J]. Circ Res, 2011, 109(6): 670-679.
[26] Li G, Kristy M, Wang Z Q, et al. STAT5 requires the N-domain for suppression of miR-15/16, induction of Bcl-2, and survival signaling in myeloproliferative disease [J]. Blood, 2010, 115(7): 1416-1424.
[27] Cimmino A, Calin G A, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting Bcl-2 [J]. Proc Natl Acad Sci USA, 2005, 102(39): 13944-13949.

[28] Eulalio A, Mano M, Dal F M, et al. Functional screening identifies miRNA inducing cardiac regeneration [J]. Nature, 2012, 492: 376-381.
[29] Chen J, Huang Z P, Seok H Y, et al. miR-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts [J]. Circ Res, 2013, 112: 1557-1566.
[30] Tian Y, Liu Y, Wang T, et al. A microRNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice [J]. Science Translational Medicine, 2015, 7: 279-291.
[31] Qian L, Huang Y, Spencer C I, et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes [J]. Nature, 2012, 485: 593-598.
[32] Song K, Nam Y J, Luo X, et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors [J]. Nature, 2012, 485: 599-604.
[33] Nam Y J, Song K, Luo X, et al. Reprogramming of human fibroblasts toward a cardiac fate [J]. Proc Natl Acad Sci USA, 2013, 110: 5588-5593.
[34] Tilanthi M J, Elizabeth A F, Lunan Z, et al. MicroRNA induced cardiac reprogramming in vivo [J]. Circ Res, 2016, DOI: 10.1161/circresaha.116.304510.
[35] Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large noncoding RNAs in mammals [J]. Nature, 2009, 458(7235): 223-227.
[36] Yadava R S, Frenzel C D, Yu Q, et al. RNA toxicity in myotonic muscular dystrophy induces Nkx2.5 expression [J]. Nat Genet, 2008, 40(1): 61-68.
[37] Freedrichs F, Zugak C, Rauch G J, et al. HBEGF, SRA1, and IK: three cosegregating genes as determinants of cardiomyopathy [J]. Genome Res, 2009, 19(3): 395-403.
[38] Cesana M, Cacchiarelli D, Legnini I, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA [J]. Cell, 2011, 147(2): 358-369.
[39] Klattenhoff C A, Scheuermann J C, Surface L E, et al. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment [J]. Cell, 2013, 152(3): 570-583.
[40] Grote P, Wittler L, Hendrix D, et al. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse [J]. Dev Cell, 2013, 24(2): 206-214.
[41] Han P, Li W, Lin C H, et al. A long noncoding RNA protects the heart from pathological hypertrophy [J]. Nature, 2014, 514(7520): 102-106.
[42] Regalla K, Christophe B, Ingo V, et al. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure [J]. Circ Res, 2014, 114(10): 1569-1575.
[43] Wang K, Liu F, Zhou L Y, et al. The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489 [J]. Circ Res, 2014, 114(9): 1377-1388.
[44] Zhou Q, Chuang A C, Huang X R, et al. Identification of novel long noncoding RNAs associated  with TGF /smad3-mediated renal inflammation and fibrosis by RNA sequencing [J]. Am J Pathol, 2014, 184(2): 409-417.

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