miR‑124 inhibits cardiomyocyte apoptosis in myocardial ischaemia‑reperfusion injury by activating mitochondrial calcium uniporter regulator 1

Guo,Linlin; Liu,Chaoying; Jiang,Chunyan; Dong,Yanhan; Htet Htet Aung,Lynn; Ding,Han; Gao,Yanyan

doi:10.3892/mmr.2023.13031

miR‑124 inhibits cardiomyocyte apoptosis in myocardial ischaemia‑reperfusion injury by activating mitochondrial calcium uniporter regulator 1

Authors:
- Linlin Guo
- Chaoying Liu
- Chunyan Jiang
- Yanhan Dong
- Lynn Htet Htet Aung
- Han Ding
- Yanyan Gao
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Affiliations: Department of Cardiovascular Medicine, The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266071, P.R. China, Oncology Department, The People's Hospital of Rizhao, Rizhao, Shandong 276827, P.R. China, Experimental Animal Center, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, P.R. China, Institute for Translational Medicine, Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China
Published online on: June 13, 2023 https://doi.org/10.3892/mmr.2023.13031
Article Number: 144

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Abstract

Mitochondria‑mediated apoptosis is the primary cause of cardiomyocyte death. Therefore, mitochondria are a key target for treating myocardial injury. Mitochondrial calcium uniporter regulator 1 (MCUR1)‑mediated mitochondrial calcium homeostasis markedly promotes cell proliferation and resistance to apoptosis. However, whether MCUR1 is involved in regulation of cardiomyocyte apoptosis during myocardial ischaemia‑reperfusion remains unknown. microRNA‑124 (miR‑124) is upregulated in cardiovascular disease, suggesting a key role for miR‑124 in the cardiovascular system. Whether miR‑124 affects cardiomyocyte apoptosis and myocardial infarction is not well understood. Western blot showed that miR‑124 and MCUR1 were upregulated in cardiomyocyte apoptosis induced by hydrogen peroxide (H₂O₂). Flow cytometry assay of cell apoptosis showed that miR‑124 inhibited cardiomyocyte apoptosis by activating MCUR1 following H2O2 treatment. The dual‑luciferase reporter assay confirmed binding of miR‑124 to MCUR1 3'‑UTR and subsequent activation of MCUR1. FISH assay revealed the entry of miR‑124 into the cell nucleus. Therefore, MCUR1 was identified as a novel target of miR‑124, and it was shown that the miR‑124‑MCUR1 axis modulated cardiomyocyte apoptosis induced by H₂O₂ in vitro. The results indicated induced expression of miR‑124 during acute myocardial infarction and its transport to the nucleus. In the nucleus, miR‑124 transcriptionally activated MCUR1 by binding to its enhancers. These findings reveal a role of miR‑124 as a biomarker for myocardial injury and infarction.

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1	De Luca G, Suryapranata H, Ottervanger JP and Antman EM: Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: Every minute of delay counts. Circulation. 109:1223–1225. 2004. View Article : Google Scholar : PubMed/NCBI
2	Heusch G: Cardioprotection: Chances and challenges of its translation to the clinic. Lancet. 381:166–175. 2013. View Article : Google Scholar : PubMed/NCBI
3	Kumfu S, Chattipakorn S, Fucharoen S and Chattipakorn N: Mitochondrial calcium uniporter blocker prevents cardiac mitochondrial dysfunction induced by iron overload in thalassemic mice. Biometals. 25:1167–1175. 2012. View Article : Google Scholar : PubMed/NCBI
4	Sripetchwandee J, Sanit J, Chattipakorn N and Chattipakorn SC: Mitochondrial calcium uniporter blocker effectively prevents brain mitochondrial dysfunction caused by iron overload. Life Sci. 92:298–304. 2013. View Article : Google Scholar : PubMed/NCBI
5	De Marchi E, Bonora M, Giorgi C and Pinton P: The mitochondrial permeability transition pore is a dispensable element for mitochondrial calcium efflux. Cell Calcium. 56:1–13. 2014. View Article : Google Scholar : PubMed/NCBI
6	Giorgi C, Bonora M, Sorrentino G, Missiroli S, Poletti F, Suski JM, Galindo Ramirez F, Rizzuto R, Di Virgilio F, Zito E, et al: p53 at the endoplasmic reticulum regulates apoptosis in a Ca²⁺-dependent manner. Proc Natl Acad Sci USA. 112:1779–1784. 2015. View Article : Google Scholar : PubMed/NCBI
7	Cortassa S, Aon MA, Marbán E, Winslow RL and O'Rourke B: An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics. Biophys J. 84:2734–2755. 2003. View Article : Google Scholar : PubMed/NCBI
8	Vieira HL and Kroemer G: Pathophysiology of mitochondrial cell death control. Cell Mol Life Sci. 56:971–976. 1999. View Article : Google Scholar : PubMed/NCBI
9	Moreau B, Nelson C and Parekh AB: Biphasic regulation of mitochondrial Ca²⁺ uptake by cytosolic Ca²⁺ concentration. Curr Biol. 16:1672–1677. 2006. View Article : Google Scholar : PubMed/NCBI
10	Marchi S, Patergnani S, Missiroli S, Morciano G, Rimessi A, Wieckowski MR, Giorgi C and Pinton P: Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death. Cell Calcium. 69:62–72. 2018. View Article : Google Scholar : PubMed/NCBI
11	Granatiero V, De Stefani D and Rizzuto R: Mitochondrial calcium handling in physiology and disease. Adv Exp Med Biol. 982:25–47. 2017. View Article : Google Scholar : PubMed/NCBI
12	Pan S, Ryu SY and Sheu SS: Distinctive characteristics and functions of multiple mitochondrial Ca²⁺ influx mechanisms. Sci China Life Sci. 54:763–769. 2011. View Article : Google Scholar : PubMed/NCBI
13	Drago I, Pizzo P and Pozzan T: After half a century mitochondrial calcium in- and efflux machineries reveal themselves. EMBO J. 30:4119–4125. 2011. View Article : Google Scholar : PubMed/NCBI
14	Kirichok Y, Krapivinsky G and Clapham DE: The mitochondrial calcium uniporter is a highly selective ion channel. Nature. 427:360–364. 2004. View Article : Google Scholar : PubMed/NCBI
15	Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, et al: Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature. 476:341–345. 2011. View Article : Google Scholar : PubMed/NCBI
16	De Stefani D, Raffaello A, Teardo E, Szabò I and Rizzuto R: A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature. 476:336–340. 2011. View Article : Google Scholar : PubMed/NCBI
17	Docampo R and Lukeš J: Trypanosomes and the solution to a 50-year mitochondrial calcium mystery. Trends Parasitol. 28:31–37. 2012. View Article : Google Scholar : PubMed/NCBI
18	Mallilankaraman K, Doonan P, Cárdenas C, Chandramoorthy HC, Müller M, Miller R, Hoffman NE, Gandhirajan RK, Molgó J, Birnbaum MJ, et al: MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival. Cell. 151:630–644. 2012. View Article : Google Scholar : PubMed/NCBI
19	Mallilankaraman K, Cardenas C, Doonan P, Chandramoorthy H, Irrinki K, Golenar T, Csordas G, Madireddi P, Yang J, Miller R, et al: MCUR1 is an essential component of mitochondrial Ca²⁺ uptake that regulates cellular metabolism. Biophys J. 104:616a2013. View Article : Google Scholar
20	Plovanich M, Bogorad RL, Sancak Y, Kamer KJ, Strittmatter L, Li AA, Girgis HS, Kuchimanchi S, De Groot J, Speciner L, et al: MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PLoS One. 8:e557852013. View Article : Google Scholar : PubMed/NCBI
21	Calderon MR, Verway M, Benslama RO, Birlea M, Bouttier M, Dimitrov V, Mader S and White JH: Ligand-dependent corepressor contributes to transcriptional repression by C2H2 zinc-finger transcription factor ZBRK1 through association with KRAB-associated protein-1. Nucleic Acids Res. 42:7012–7027. 2014. View Article : Google Scholar : PubMed/NCBI
22	Kastenhuber ER and Lowe SW: Putting p53 in context. Cell. 170:1062–1078. 2017. View Article : Google Scholar : PubMed/NCBI
23	Tian C, Xing G, Xie P, Lu K, Nie J, Wang J, Li L, Gao M, Zhang L and He F: KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis. Nat Cell Biol. 11:580–591. 2009. View Article : Google Scholar : PubMed/NCBI
24	Yuan L, Tian C, Wang H, Song S, Li D, Xing G, Yin Y, He F and Zhang L: Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis. EMBO Rep. 13:363–370. 2012. View Article : Google Scholar : PubMed/NCBI
25	Ren T, Wang J, Zhang H, Yuan P, Zhu J, Wu Y, Huang Q, Guo X, Zhang J, Ji L, et al: MCUR1-mediated mitochondrial calcium signaling facilitates cell survival of hepatocellular carcinoma via reactive oxygen species-dependent P53 degradation. Antioxid Redox Signal. 28:1120–1136. 2018. View Article : Google Scholar : PubMed/NCBI
26	García-Rivas Gde J, Carvajal K, Correa F and Zazueta C: Ru360, a specific mitochondrial calcium uptake inhibitor, improves cardiac post-ischaemic functional recovery in rats in vivo. Br J Pharmacol. 149:829–837. 2006. View Article : Google Scholar : PubMed/NCBI
27	Joiner MLA, Koval OM, Li J, He BJ, Allamargot C, Gao Z, Luczak ED, Hall DD, Fink BD, Chen B, et al: CaMKII determines mitochondrial stress responses in heart. Nature. 491:269–273. 2012. View Article : Google Scholar : PubMed/NCBI
28	Liang N, Wang P, Wang S, Li S, Li Y, Wang J and Wang M: Role of mitochondrial calcium uniporter in regulating mitochondrial fission in the cerebral cortexes of living rats. J Neural Transm (Vienna). 121:593–600. 2014. View Article : Google Scholar : PubMed/NCBI
29	Zhang L, Gao X, Yuan X, Dong H, Zhang Z and Wang S: Mitochondrial calcium uniporter opener spermine attenuates the cerebral protection of diazoxide through apoptosis in rats. J Stroke Cerebrovasc Dis. 23:829–835. 2014. View Article : Google Scholar : PubMed/NCBI
30	Yan H, Zhang D, Hao S, Li K and Hang CH: Role of mitochondrial calcium uniporter in early brain injury after experimental subarachnoid hemorrhage. Mol Neurobiol. 52:1637–1647. 2015. View Article : Google Scholar : PubMed/NCBI
31	Liao Y, Hao Y, Chen H, He Q, Yuan Z and Cheng J: Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death. Protein Cell. 6:434–442. 2015. View Article : Google Scholar : PubMed/NCBI
32	Santulli G, Xie W, Reiken SR and Marks AR: Mitochondrial calcium overload is a key determinant in heart failure. Proc Natl Acad Sci USA. 112:11389–11394. 2015. View Article : Google Scholar : PubMed/NCBI
33	Bell JR, Erickson JR and Delbridge LM: Ca(2+)/calmodulin dependent kinase II: A critical mediator in determining reperfusion outcomes in the heart? Clin Exp Pharmacol Physiol. 41:940–946. 2014. View Article : Google Scholar : PubMed/NCBI
34	Icli B, Wara AKM, Moslehi J, Sun X, Plovie E, Cahill M, Marchini JF, Schissler A, Padera RF, Shi J, et al: MicroRNA-26a regulates pathological and physiological angiogenesis by targeting BMP/SMAD1 signaling. Circ Res. 113:1231–1241. 2013. View Article : Google Scholar : PubMed/NCBI
35	Hu S, Huang M, Li Z, Jia F, Ghosh Z, Lijkwan MA, Fasanaro P, Sun N, Wang X, Martelli F, et al: MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. Circulation. 122 (11 Suppl):S124–S131. 2010. View Article : Google Scholar : PubMed/NCBI
36	Zhang X, Yoon JY, Morley M, McLendon JM, Mapuskar KA, Gutmann R, Mehdi H, Bloom HL, Dudley SC, Ellinor PT, et al: A common variant alters SCN5A-miR-24 interaction and associates with heart failure mortality. J Clin Invest. 128:1154–1163. 2018. View Article : Google Scholar : PubMed/NCBI
37	Demkes CJ and van Rooij E: MicroRNA-146a as a regulator of cardiac energy metabolism. Circulation. 136:762–764. 2017. View Article : Google Scholar : PubMed/NCBI
38	Sun Y, Luo ZM, Guo XM, Su DF and Liu X: An updated role of microRNA-124 in central nervous system disorders: A review. Front Cell Neurosci. 9:1932015. View Article : Google Scholar : PubMed/NCBI
39	Bao Q, Chen L, Li J, Zhao M, Wu S, Wu W and Liu X: Role of microRNA-124 in cardiomyocyte hypertrophy induced by angiotensin II. Cell Mol Biol (Noisy-le-grand). 63:23–27. 2017. View Article : Google Scholar : PubMed/NCBI
40	Zhang L, Chen Q, An W, Yang F, Maguire EM, Chen D, Zhang C, Wen G, Yang M, Dai B, et al: Novel pathological role of hnRNPA1 (heterogeneous nuclear Ribonucleoprotein A1) in vascular smooth muscle cell function and Neointima hyperplasia. Arterioscler Thromb Vasc Biol. 37:2182–2194. 2017. View Article : Google Scholar : PubMed/NCBI
41	Han F, Chen Q, Su J, Zheng A, Chen K, Sun S, Wu H, Jiang L, Xu X, Yang M, et al: MicroRNA-124 regulates cardiomyocyte apoptosis and myocardial infarction through targeting Dhcr24. J Mol Cell Cardiol. 132:178–188. 2019. View Article : Google Scholar : PubMed/NCBI
42	de Ronde MWJ, Kok MGM, Moerland PD, Van den Bossche J, Neele AE, Halliani A, van der Made I, de Winther MPJ, Meijers JCM, Creemers EE and Pinto-Sietsma SJ: High miR-124-3p expression identifies smoking individuals susceptible to atherosclerosis. Atherosclerosis. 263:377–384. 2017. View Article : Google Scholar : PubMed/NCBI
43	Devaux Y, Dankiewicz J, Salgado-Somoza A, Stammet P, Collignon O, Gilje P, Gidlöf O, Zhang L, Vausort M, Hassager C, et al: Association of circulating MicroRNA-124-3p levels with outcomes after out-of-hospital cardiac arrest: A substudy of a randomized clinical trial. JAMA Cardiol. 1:305–313. 2016. View Article : Google Scholar : PubMed/NCBI
44	Gilje P, Gidlöf O, Rundgren M, Cronberg T, Al-Mashat M, Olde B, Friberg H and Erlinge D: The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest. Crit Care. 18:R402014. View Article : Google Scholar : PubMed/NCBI
45	Gacoń J, Kabłak-Ziembicka A, Stępień E, Enguita FJ, Karch I, Derlaga B, Żmudka K and Przewłocki T: Decision-making microRNAs (miR-124, −133a/b, −34a and −134) in patients with occluded target vessel in acute coronary syndrome. Kardiol Pol. 74:280–288. 2016. View Article : Google Scholar : PubMed/NCBI
46	Ghafouri-Fard S, Shoorei H, Bahroudi Z, Abak A, Majidpoor J and Taheri M: An update on the role of miR-124 in the pathogenesis of human disorders. Biomed Pharmacother. 135:1111982021. View Article : Google Scholar : PubMed/NCBI
47	Liu Y, Li Y, Ni J, Shu Y, Wang H and Hu T: MiR-124 attenuates doxorubicin-induced cardiac injury via inhibiting p66Shc-mediated oxidative stress. Biochem Biophys Res Commun. 521:420–426. 2020. View Article : Google Scholar : PubMed/NCBI
48	Zhu P, Li H, Zhang A, Li Z, Zhang Y, Ren M, Zhang Y and Hou Y: MicroRNAs sequencing of plasma exosomes derived from patients with atrial fibrillation: miR-124-3p promotes cardiac fibroblast activation and proliferation by regulating AXIN1. J Physiol Biochem. 78:85–98. 2022. View Article : Google Scholar : PubMed/NCBI
49	Hescheler J, Meyer R, Plant S, Krautwurst D, Rosenthal W and Schultz G: Morphological, biochemical, and electrophysiological characterization of a clonal cell (H9c2) line from rat heart. Circ Res. 69:1476–1486. 1991. View Article : Google Scholar : PubMed/NCBI
50	Shimada Y, Fischman DA and Moscona AA: The fine structure of embryonic chick skeletal muscle cells differentiated in vitro. J Cell Biol. 35:445–453. 1967. View Article : Google Scholar : PubMed/NCBI
51	Forero DA, González-Giraldo Y, Castro-Vega LJ and Barreto GE: qPCR-based methods for expression analysis of miRNAs. Biotechniques. 67:192–199. 2019. View Article : Google Scholar : PubMed/NCBI
52	Shin S, Jung Y, Uhm H, Song M, Son S, Goo J, Jeong C, Song JJ, Kim VN and Hohng S: Quantification of purified endogenous miRNAs with high sensitivity and specificity. Nat Commun. 11:60332020. View Article : Google Scholar : PubMed/NCBI
53	John B, Enright AJ, Aravin A, Tuschl T, Sander C and Marks DS: Human MicroRNA targets. PLoS Biol. 2:e3632004. View Article : Google Scholar : PubMed/NCBI
54	Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP and Burge CB: Prediction of mammalian microRNA targets. Cell. 115:787–798. 2003. View Article : Google Scholar : PubMed/NCBI
55	Lee Y and Gustafsson AB: Role of apoptosis in cardiovascular disease. Apoptosis. 14:536–548. 2009. View Article : Google Scholar : PubMed/NCBI
56	Bialik S, Geenen DL, Sasson IE, Cheng R, Horner JW, Evans SM, Lord EM, Koch CJ and Kitsis RN: Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53. J Clin Invest. 100:1363–1372. 1997. View Article : Google Scholar : PubMed/NCBI
57	Xiao M, Li J, Li W, Wang Y, Wu F, Xi Y, Zhang L, Ding C, Luo H, Li Y, et al: MicroRNAs activate gene transcription epigenetically as an enhancer trigger. RNA Biol. 14:1326–1334. 2017. View Article : Google Scholar : PubMed/NCBI
58	Lu L, Zhou L, Chen EZ, Sun K, Jiang P, Wang L, Su X, Sun H and Wang H: A novel YY1-miR-1 regulatory circuit in skeletal myogenesis revealed by genome-wide prediction of YY1-miRNA network. PLoS One. 7:e275962012. View Article : Google Scholar : PubMed/NCBI
59	Lee BK, Bhinge AA and Iyer VR: Wide-ranging functions of E2F4 in transcriptional activation and repression revealed by genome-wide analysis. Nucleic Acids Res. 39:3558–3573. 2011. View Article : Google Scholar : PubMed/NCBI
60	Guimbellot JS, Erickson SW, Mehta T, Wen H, Page GP, Sorscher EJ and Hong JS: Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis. BMC Med Genomics. 2:152009. View Article : Google Scholar : PubMed/NCBI
61	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
62	Xu J, Zheng Y, Wang L, Liu Y, Wang X, Li Y and Chi G: miR-124: A promising therapeutic target for central nervous system injuries and diseases. Cell Mol Neurobiol. 42:2031–2053. 2022. View Article : Google Scholar : PubMed/NCBI
63	Qin Z, Wang PY, Su DF and Liu X: miRNA-124 in immune system and immune disorders. Front Immunol. 7:4062016. View Article : Google Scholar : PubMed/NCBI
64	Yang J, Zhang X, Chen X, Wang L and Yang G: Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia. Mol Ther Nucleic Acids. 7:278–287. 2017. View Article : Google Scholar : PubMed/NCBI
65	Cai B, Li J, Wang J, Luo X, Ai J, Liu Y, Wang N, Liang H, Zhang M, Chen N, et al: microRNA-124 regulates cardiomyocyte differentiation of bone marrow-derived mesenchymal stem cells via targeting STAT3 signaling. Stem Cells. 30:1746–1755. 2012. View Article : Google Scholar : PubMed/NCBI
66	Devaux Y and Stammet P: Cardiolinc^™ network: What's new in prognostication after cardiac arrest: microRNAs? Intensive Care Med. 44:897–899. 2018. View Article : Google Scholar : PubMed/NCBI
67	Das E, Jana NR and Bhattacharyya NP: MicroRNA-124 targets CCNA2 and regulates cell cycle in STHdh(Q111)/Hdh(Q111) cells. Biochem Biophys Res Commun. 437:217–224. 2013. View Article : Google Scholar : PubMed/NCBI
68	Taniguchi K, Sugito N, Kumazaki M, Shinohara H, Yamada N, Nakagawa Y, Ito Y, Otsuki Y, Uno B, Uchiyama K and Akao Y: MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer. Cancer Lett. 363:17–27. 2015. View Article : Google Scholar : PubMed/NCBI
69	Liang YN, Tang YL, Ke ZY, Chen YQ, Luo XQ, Zhang H and Huang LB: MiR-124 contributes to glucocorticoid resistance in acute lymphoblastic leukemia by promoting proliferation, inhibiting apoptosis and targeting the glucocorticoid receptor. J Steroid Biochem Mol Biol. 172:62–68. 2017. View Article : Google Scholar : PubMed/NCBI
70	Mallilankaraman K, Cárdenas C, Doonan PJ, Chandramoorthy HC, Irrinki KM, Golenár T, Csordás G, Madireddi P, Yang J, Müller M, et al: MCUR1 is an essential component of mitochondrial Ca²⁺ uptake that regulates cellular metabolism. Nat Cell Biol. 14:1336–1343. 2012. View Article : Google Scholar : PubMed/NCBI
71	Tomar D, Dong Z, Shanmughapriya S, Koch DA, Thomas T, Hoffman NE, Timbalia SA, Goldman SJ, Breves SL, Corbally DP, et al: MCUR1 is a scaffold factor for the MCU complex function and promotes mitochondrial bioenergetics. Cell Rep. 15:1673–1685. 2016. View Article : Google Scholar : PubMed/NCBI
72	Romero-Garcia S and Prado-Garcia H: Mitochondrial calcium: Transport and modulation of cellular processes in homeostasis and cancer (review). Int J Oncol. 54:1155–1167. 2019.PubMed/NCBI
73	Kwong JQ: The mitochondrial calcium uniporter in the heart: Energetics and beyond. J Physiol. 595:3743–3751. 2017. View Article : Google Scholar : PubMed/NCBI
74	Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 79:351–379. 2010. View Article : Google Scholar : PubMed/NCBI
75	Pasquinelli AE: MicroRNAs and their targets: Recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 13:271–282. 2012. View Article : Google Scholar : PubMed/NCBI
76	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
77	Place RF, Li LC, Pookot D, Noonan EJ and Dahiya R: MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci USA. 105:1608–1613. 2008. View Article : Google Scholar : PubMed/NCBI
78	Dvinge H, Git A, Gräf S, Salmon-Divon M, Curtis C, Sottoriva A, Zhao Y, Hirst M, Armisen J, Miska EA, et al: The shaping and functional consequences of the microRNA landscape in breast cancer. Nature. 497:378–382. 2013. View Article : Google Scholar : PubMed/NCBI
79	Zou Q, Liang Y, Luo H and Yu W: miRNA-mediated RNAa by targeting enhancers. Adv Exp Med Biol. 983:113–125. 2017. View Article : Google Scholar : PubMed/NCBI
80	Liu H, Lei C, He Q, Pan Z, Xiao D and Tao Y: Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer. Mol Cancer. 17:642018. View Article : Google Scholar : PubMed/NCBI
81	Vaschetto LM: miRNA activation is an endogenous gene expression pathway. RNA Biol. 15:826–828. 2018.PubMed/NCBI