心肌梗死是常见的心血管疾病，导致心肌细胞丢失，肉芽组织和胶原纤维化代替造成心肌病理性重构，逐渐进展为心脏衰竭。近几年对心肌细胞增殖的研究证实成年哺乳动物心肌细胞仍保留增殖能力，并在心肌损伤后进行分裂增殖。然而，心肌细胞增殖效率低下，不能满足受损心肌修复的需要，因此促进内源性心肌细胞增殖成为心脏再生领域的研究热点。本文作者简单概述非编码RNA （ncRNA）在心肌细胞增殖中的作用，探究其在心肌梗死以及心脏再生方面的治疗可行性。

[1] 王增武, 胡盛寿.《中国心血管健康与疾病报告2019》要点解读[J].中国心血管杂志, 2020, 25(5):401-410.
[2] ROTH G A, MENSAH G A, JOHNSON C O, et al.Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019:Update From the GBD 2019 Study[J].J Am Coll Cardiol, 2020, 76(25):2982-3021.
[3] VOGEL B, CLAESSEN B E, ARNOLD S V, et al.ST-segment elevation myocardial infarction[J].Nat Rev Dis Primers, 2019, 5(1):39.
[4] JENNINGS R B.Historical perspective on the pathology of myocardial ischemia/reperfusion injury[J].Circ Res, 2013, 113(4):428-438.
[5] JENNINGS RB M C, STEENBERGEN C Jr, REIMER K A.Development of cell injury in sustained acute ischemia[J].Circulation, 1990, 82(3 Suppl):II2-12.
[6] PORRELLO E R, OLSON E N.A neonatal blueprint for cardiac regeneration[J].Stem Cell Res, 2014, 13(3PtB):556-570.
[7] BERGMANN O, BHARDWAJ R D, BERNARD S, et al.Evidence for cardiomyocyte renewal in humans[J].Science, 2009, 324(5923):98-102.
[8] HAUBNER B J, SCHNEIDER J, SCHWEIGMANN U, et al.Functional recovery of a human neonatal heart after severe myocardial infarction[J].Circ Res, 2016, 118(2):216-221.
[9] PONNUSAMY M, LIU F, ZHANG Y H, et al.Long noncoding RNA CPR(cardiomyocyte proliferation regulator) regulates cardiomyocyte proliferation and cardiac repair[J].Circulation, 2019, 139(23):2668-2684.
[10] XIN M, OLSON E N, BASSEL-DUBY R.Mending broken hearts:cardiac development as a basis for adult heart regeneration and repair[J].Nat Rev Mol Cell Biol, 2013, 14(8):529-541.
[11] LEE R C, FEINBAUM R L, AMBROS V.The C.elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14[J].Cell, 1993, 75(5):843-854.
[12] THUM T, MAYR M.Review focus on the role of microRNA in cardiovascular biology and disease[J].Cardiovasc Res, 2012, 93(4):543-544.
[13] EULALIO A, MANO M, DAL FERRO M, et al.Functional screening identifies miRNAs inducing cardiac regeneration[J].Nature, 2012, 492(7429):376-381.
[14] TAO Y, ZHANG H, HUANG S, et al.miR-199a-3p promotes cardiomyocyte proliferation by inhibiting Cd151 expression[J].Biochem Biophys Res Commun, 2019, 516(1):28-36.
[15] GABISONIA K, PROSDOCIMO G, AQUARO G D, et al.MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs[J].Nature, 2019, 569(7756):418-422.
[16] 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.
[17] PORRELLO E R, MAHMOUD A I, SIMPSON E, et al.Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family[J].Proc Natl Acad Sci U S A, 2013, 110(1):187-192.
[18] ZHANG Y, MATSUSHITA N, EIGLER T, et al.Targeted microRNA interference promotes postnatal cardiac cell cycle re-entry[J].J Regen Med, 2013, 2:2.
[19] CAO X, WANG J, WANG Z, et al.MicroRNA profiling during rat ventricular maturation:a role for miR-29a in regulating cardiomyocyte cell cycle re-entry[J].FEBS Lett, 2013, 587(10):1548-1555.
[20] LIU N, BEZPROZVANNAYA S, WILLIAMS A H, et al.microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart[J].Genes Dev, 2008, 22(23):3242-3254.
[21] DIEZ-CUNADO M, WEI K, BUSHWAY P J, et al.miRNAs that induce human cardiomyocyte proliferation converge on the hippo pathway[J].Cell Rep, 2018, 23(7):2168-2174.
[22] XIN M, KIM Y, SUTHERLAND L B, et al.Hippo pathway effector Yap promotes cardiac regeneration[J].Proc Natl Acad Sci U S A, 2013, 110(34):13839-13844.
[23] WANG J, LIU S, HEALLEN T, et al.The Hippo pathway in the heart:pivotal roles in development, disease, and regeneration[J].Nat Rev Cardiol, 2018, 15(11):672-684.
[24] VAN ROOIJ E, PURCELL A L, LEVIN A A.Developing microRNA therapeutics[J].Circ Res, 2012, 110(3):496-507.
[25] ZHAO L, BORIKOVA A L, BEN-YAIR R, et al.Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration[J].Proc Natl Acad Sci U S A, 2014, 111(4):1403-1408.
[26] STRUHL K.Transcriptional noise and the fidelity of initiation by RNA polymerase[J].Nat Struct Mol Biol, 2007, 14(2):103-105.
[27] GUPTA R A, SHAH N, WANG K C, et al.Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis[J].Nature, 2010, 464(7291):1071-1076.
[28] TSAI M C, MANOR O, WAN Y, et al.Long noncoding RNA as modular scaffold of histone modification complexes[J].Science, 2010, 329(5992):689-693.
[29] TIAN D, SUN S, LEE J T.The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation[J].Cell, 2010, 143(3):390-403.
[30] ROBINSON E K, COVARRUBIAS S, CARPENTER S.The how and why of lncRNA function:an innate immune perspective[J].Biochim Biophys Acta Gene Regul Mech, 2020, 1863(4):194419.
[31] THAM Y K, BERNARDO B C, OOI J Y, et al.Pathophysiology of cardiac hypertrophy and heart failure:signaling pathways and novel therapeutic targets[J].Arch Toxicol, 2015, 89(9):1401-1438.
[32] CHEN Y, LI X, LI B, et al.Long non-coding RNA ECRAR triggers post-natal myocardial regeneration by activating ERK1/2 signaling[J].Mol Ther, 2019, 27(1):29-45.
[33] CHEN G, LI H, LI X, et al.Loss of long non-coding RNA CRRL promotes cardiomyocyte regeneration and improves cardiac repair by functioning as a competing endogenous RNA[J].J Mol Cell Cardiol, 2018, 122:152-164.
[34] CANZIO D, NWAKEZE C L, HORTA A, et al.Antisense lncRNA transcription mediates DNA demethylation to drive stochastic protocadherin α promoter choice[J].Cell, 2019, 177(3):639-653.e15.
[35] LI B, HU Y, LI X, et al.Sirt1 antisense long noncoding RNA promotes cardiomyocyte proliferation by enhancing the stability of sirt1[J].J Am Heart Assoc, 2018, 7(21):e009700.
[36] CHEN Y M, ZHENG Y L, SU X, et al.Crosstalk between microRNAs and circular RNAs in human diseases:a bibliographic study[J].Front Cell Dev Biol, 2021, 9:754880.
[37] ZHENG Q, BAO C, GUO W, et al.Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs[J].Nat Commun, 2016, 7:11215.
[38] 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.
[39] AUFIERO S, RECKMAN Y J, PINTO Y M, et al.Circular RNAs open a new chapter in cardiovascular biology[J].Nat Rev Cardiol, 2019, 16(8):503-514.
[40] HUANG S, LI X, ZHENG H, et al.Loss of super-enhancer-regulated circRNA Nfix induces cardiac regeneration after myocardial infarction in adult mice[J].Circulation, 2019, 139(25):2857-2876.
[41] TIAN Y, LIU Y, WANG T, et al.A microRNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice[J].Sci Transl Med, 2015, 7(279):279ra38.
[42] PANDEY R, YANG Y, JACKSON L, et al.MicroRNAs regulating meis1 expression and inducing cardiomyocyte proliferation[J].Cardiovasc Regen Med, 2016, 3:e1468.