Table II.

Target genes associated with cardiomyocyte-derived microRNAs

microRNA	Target gene	Activity/significance	Reference
miR-1	HDAC4, MEF2C	–Promote mesoderm formation and suppress non-muscle gene expression in ESC –Strongly enhance myogenesis by increase in expression of myogenin and MHCs, MyoD, MEF2 and skeletal α-actin	[19, 32]
miR-133a	SRF	–Promotes mesoderm formation and suppresses non-muscle gene expression in ESC –Enhances myoblast proliferation by repressing SRF	[20, 32, 34]
miR-128a	Isl1, Sfrp5, Hcn4, Irx4	–Postnatal heart growth by modulating cardiomyocyte proliferation during early cardiogenesis –Upregulating the transcription factors of cardiac progenitor cells –Marking ventricular progenitors	[21, 57, 58, 59]
cluster of miR-17-92	PTEN, CDK1	Regulation of cardiomyocyte proliferation in embryonic, postnatal, and adult hearts	[23, 60, 61]
miR-15 miR-16	C/EBPβ, IGF1	Protection/downregulation of cardiac hypertrophy	[54]
miR-208b	β-MHC, Sox6, Purβ, Sp3, HP1β	–Dominant role in the specification of muscle fiber identity by activating slow and repressing fast myofiber gene programs –Upregulation of slow MHCs in adult heart	[25] [37]
miR-499	Sox6, cyclin D1	Inhibition of cell proliferation and promotion of cell apoptosis in P19CL6 cells and cardiomyocytes	[38] [39]
miR-133b	PTBP1, TAGLN2	Alleviates apoptosis and cardiac fibrosis, modulates collagen deposition	[53]
miR-143/145	HK2	Addresses G6PD, PPP pathways and p62. Activation of these signaling pathways induces a reductive redox shift, resulting in cardiomyopathy	[55]
miR-155	NEDD4	Cardioprotective against cardiomyocyte apoptosis; modulates myofibroblast density	[56]
miR-218	REST	Regulates cardiac differentiation of embryonic stem cells by regulating the Wnt/β-catenin signaling pathway and GATA4	[63]
miR-124	STAT3	–Downregulation of cardiac-specific markers-ANP, TnT, and α-MHC proteins; –Regulation of myogenic differentiation of BMSCs by targeting STAT3 mRNA	[64, 65]
miR-21	Ajuba/Isl1	Differentiation of BMSCs into cardiomyocyte-like cells; contributes to formation and maintenance of cell-cell connections and supports cell division and migration	[66]
miR-31	CAMK2D, YWHAE	Promotes loss of dystrophin and nNOS in human	[67]
miR-103/107	PANKs, FADD	Modulates mitochondrial concentration; regulates systemic glucose metabolism; H2O2-induced necrosis	[68, 69]
miR-200b	GATA-4	Transcription factor; regulation of developmental processes of the heart, cardiac myocyte proliferation, differentiation and survival	[70]

ANP – atrial natriuretic peptide, BMSCs – bone marrow-derived mesenchymal stem cells, CAMK2D – calcium/calmodulin dependent protein kinase II delta, CDK1 – cyclin dependent kinase 1, C/EBPβ – CCAAT enhancer binding protein beta, ESCs – embryonic stem cells, FADD – Fas-associated via death domain, G6PD – glucose-6-phosphate dehydrogenase, GATA4 – GATA binding protein 4, Hcn4 – hyperpolarization activated cyclic nucleotide gated potassium channel 4, HDAC4 – histone deacetylase 4, HK 2 – hexokinase 2, HP1β – heterochromatin protein 1β, IGF1 – insulin-like growth factor-1, Irx4 – iroquois homeobox 4, MEF2 – myocyte-specific enhancer factor 2, MHC – myosin heavy chains, mRNA – messenger ribonucleic acid, MyoD – myoblast determination protein 1, NEDD4 – neural precursor cell expressed developmentally down-regulated protein 4, nNOS – neuronal nitric oxide synthase, PANKs – pantothenate kinases, PPP – pentose phosphate pathway, PTBP1 – polypyrimidine tract-binding protein 1, PTEN – phosphatase and tensin homolog, Purβ – purine rich element binding protein B, REST – RE1 silencing transcription factor, Sfrp5 – secreted frizzled related protein 5, Sox6 – SRY-box transcription factor 6, Sp3 – specificity protein 3, SRF – serum response factor, STAT3 – signal transducer and activator of transcription 3, TAGLN2 – transgelin 2, TnT – troponin T, YWHAE – tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon, Wnt – wingless/integrated.