MicroRNAs miR-1, miR-133a, miR-133b and miR-208 Are Dysregulated in Human Myocardial InfarctionBoštjančič E.a · Zidar N.a · Štajer D.b · Glavač D.a
aDepartment of Molecular Genetics,Institute of Pathology, Faculty of Medicine, University of Ljubljana, and bCentre for Intensive Internal Medicine, University Medical Centre, Ljubljana, Slovenia
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Article / Publication Details
Objectives: MicroRNAs (miRNAs) are noncoding single-stranded RNA molecules that regulate gene expression in physiological functions, development and disease. In recent studies, three miRNAs have been described as muscle or cardiac specific: miR-1, miR-133, and miR-208, being involved in heart development and disease; but there are limited data on their role in human myocardial infarction (MI). We therefore analyzed their expression in human MI. Methods: Autopsy samples of infarcted heart tissue from 50 patients with MI, 8 healthy trauma victims and 9 fetuses that died in utero were included. miRNAs miR-1, miR-133a/b and miR-208 were analyzed using quantitative real-time polymerase chain reaction. Results:miR-208 was upregulated, whereas miR-1 and miR-133a were downregulated in MI compared to healthy adult and fetal hearts. All four tested miRNAs were downregulated in fetal hearts compared to healthy adult hearts. Conclusions: Our study showed the involvement of muscle- and/or cardiac-specific miRNAs miR-1, miR-133a/b and miR-208 in human MI. The most significant finding was upregulation of miR-208 and downregulation of miR-1 and miR-133a in MI compared to healthy adult hearts. Some patterns of miRNA expression were similar in MI and fetal hearts, supporting the concept of cardiac gene reprogramming in the remodeling of the heart.
© 2009 S. Karger AG, Basel
- Scalbert E, Bril A: Implication of microRNAs in the cardiovascular system. Curr Opin Pharmacol 2008;8:181–188.
- Fazi F, Nervi C: MicroRNA: basic mechanisms and transcriptional regulatory networks for cell fate determination. Cardiovasc Res 2008;79:553–561.
- Williams AE: Functional aspects of animal microRNAs. Cell Mol Life Sci 2008;65:545–562.
- Chen J-F, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ: The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 2006;38:228–233.
- Liu N, Williams AH, Kim Y, McAnally J, Bezprozvannaya S, Sutherland LB, Richardson JA, Bassel-Duby R, Olson EN: An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133. Proc Natl Acad Sci USA 2007;104:20844–20849.
- Thum T, Catalucci D, Bauersachs J: MicroRNAs: novel regulators in cardiac development and disease. Cardiovasc Res 2008;79:562–570.
- Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y, Dalton ND, Elia L, Latronico MV, Høydal M, Autore C, Russo MA, Dorn GW 2nd, Ellingsen O, Ruiz-Lozano P, Peterson KL, Croce CM, Peschle C, Condorelli G: MicroRNA-133 controls cardiac hypertrophy. Nat Med 2007;13:613–618.
- Sucharov C, Bristow MR, Port JD: miRNA expression in failing human heart: functional correlates. J Mol Cell Cardiol 2008;45:185–192.
- Wang J, Xu R, Lin F, Zhang S, Zhang G, Hu S, Zheng Z: MicroRNA: novel regulators involved in the remodeling and reverse remodeling of the heart. Cardiology 2009;113:81–88.
- van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN: Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007;316:575–579.
- Yang B, Lin H, Xiao J, Lu Y, Luo X, Li B, Zhang Y, Xu C, Bai Y, Wang H, Chen G, Wang Z: The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med 2007;13:486–491.
- van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN: Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA 2008;105:3027–13032.
- Yin C, Wang X, Kukreja RC: Endogenous microRNAs induced by heat-shock reduce myocardial infarction following ischemia-reperfusion in mice. FEBS Lett 2008;582:4137–4142.
- Roy S, Khanna S, Hussain SR, Biswas S, Azad A, Rink C, Gnyawali S, Shilo S, Nuovo GJ, Sen CK: MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc Res 2009;82:21–29.
- Zidar N, Jeruc J, Balažic J, Štajer D: Neutrophils in human myocardial infarction with rupture of the free wall. Cardiovasc Pathol 2005;14:247–250.
Wong L, Kathy L, Russell I, Chen C: Endogenous controls for real-time quantitation of miRNA using TaqMan® microRNA assays. Appl Biosyst Appl Note 2007.
- Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCT method. Methods 2001;25:402–408.
- Yuan JS, Reed A, Chen F, Stewart CN Jr: Statistical analysis of real-time PCR data. BMC Bioinformatics 2006;7:85–96.
- Bravo V, Rosero S, Ricordi C, Pastori RL: Instability of miRNA and cDNAs derivatives in RNA preparations. Biochem Biophys Res Commun 2007;353:1052–1055.
- Xu C, Lu Y, Pan Z, Chu W, Luo X, Lin H, Xiao J, Shan H, Wang Z, Yang B: The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci 2007;120:3045–3052.
- Luo X, Lin H, Pan Z, Xiao J, Zhang Y, Lu Y, Yang B, Wang Z: Downregulation of miRNA-1/miRNA-133 contributes to re-expression of pacemaker channel genes HCN2 and HCN4 in hypertrophic heart. J Biol Chem 2008;283:20045–20052.
- van Rooij E, Olson EN: MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targets. J Clin Invest 2007;117:2369–2376.
- Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, Doevendans PA, Mummery CL, Borlak J, Haverich A, Gross C, Engelhardt S, Ertl G, Bauersachs J: MicroRNAs in the human heart: a clue to foetal gene reprogramming in heart failure. Circulation 2007;116:258–267.
- Callis TE, Pandya K, Seok HY, Tang RH, Tatsuguchi M, Huang ZP, Chen JF, Deng Z, Gunn B, Shumate J, Willis MS, Selzman CH, Wang D-Z: MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 2009;119:2772–2786.
Boštjančič E, Zidar N, Štajer D, Glavač D: MicroRNA miR-1 is up-regulated in remote myocardium in patients with myocardial infarction. Folia Biol, accepted.
- von Ahlfen S, Missel A, Bendrat K, Schlumpberger M: Determinants of RNA quality from FFPE samples. PLoS ONE 2007;12:e1261.
- Li J, Smyth P, Flavin R, Cahill S, Denning K, Aherne S, Guenther SM, O’Leary JJ, Sheils O: Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells. BMC Biotechnol 2007;7:36.
- Xi Y, Nakajima G, Gavin E, Morris CG, Kudo K, Hayashi K, Ju J: Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA 2007;13:1668–1674.
- Rogaev EI: Small RNAs in human brain development and disorders. Biochemistry(Mosc.) 2005;70:1404–1407.
- Zhao JJ, Hua YJ, Sun DG, Meng XX, Xiao HS, Ma X: Genome-wide microRNA profiling in human foetal nervous tissues by oligonucleotide microarray. Childs Nerv Syst 2006;22:1419–1425.
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