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Table 1 MicroRNAs inhibiting cardiomyocyte proliferation and cardiac regeneration

From: miRNA in cardiac development and regeneration

miRNA Experimental models Major findings Targets Ref.
miR-1 β-MHC-miR-1 transgenic mice Overexpression of miR-1 decreases the number of cycling cardiomyocytes, results in developmental arrest at E13.5, secondary to thin-walled ventricles and heart failure. Hand2, Ccnd1 (Zhao et al. 2005; Zhao et al. 2007; Wei et al. 2014; Gan et al. 2019)
miR-1-2−/− mice miR-1-2−/− mutants display thickening of the walls of the heart, while the increased weight may be due to hyperplasia.
miR-1 dKO mice miR-1 dKO neonatal mice display proliferating cardiomyocytes.
neonatal mouse CMs miR-1 represses cardiomyocyte G1/S phase transition.
miR133a miR-133a double-mutant mice miR-133a double-mutant mice display late embryonic or neonatal lethality due to VSDs, while the surviving mutant mice display severe deficits in cardiac contractility and die from heart failure and sudden death. The absence of miR-133a expression results in ectopic expression of smooth muscle genes in the heart and aberrant cardiomyocyte proliferation. Srf and Ccnd2 (Liu et al. 2008)
miR-15 family (miR-195, miR-15) βMHC-miR-195 transgenic mice Overexpression of miR-195 in the embryonic heart causes ventricular hypoplasia and ventricular septal defects. Chek1,
(Porrello et al. 2011a; Hullinger et al. 2012; Porrello et al. 2013)
delivery of anti- miR-15 family (LNA- miR-15 family) to neonatal mice Post-natal inhibition of miR-15 family induces cardiomyocyte proliferation, as well as cardiomyocytes displaying disorganized sarcomeric structures.
neonatal CMs Inhibition of miR-15 induces cardiomyocyte viability in response to hypoxia
delivery of miR-15 anti-miRs in hearts of both mice and pigs Inhibition of miR-15 family protectes against cardiac ischemic injury
delivery of anti- miR-15 family (LNA- miR-15 family) to neonatal mice before MI Inhibition of the miR-15 family induces cardiomyocyte proliferation and improves left ventricular systolic function.
miR-29a H9c2 cell line Overexpression of miR-29a suppresses proliferation of H9c2 cell line. CCND2 (Cao et al. 2013)
miR-99/100 and Let-7a/c adult zebrafish Injecting miR-99/100 mimics blocks cardiac regeneration, and injecting antagomir against miR-99/100 promots cardiomyocyte proliferation and cardiac growth smarca5 and fntb (Aguirre et al. 2014)
a murine model of MI Inhibition of miR-99/100 and Let-7a/c induces the myocardial tissue to a partially dedifferentiated proliferative state after cardiac injury.
miR-101a adult zebrafish Inhibition of miR-101a levels at the onset of cardiac injury enhances CM proliferation, while prolonged inhibition of miR-101a activity stimulates new muscle synthesis but with defects in scar tissue clearance. fosab (cfos) (Beauchemin et al. 2015)
miR-34a delivery of miR-34a mimic to the myocardium at the time of MI Overexpression of miR-34a inhibits functional post-MI recovery in neonatal mouse hearts. Bcl2, Ccnd1, and Sirt1 (Yang et al. 2015)
delivery of anti-miR-34a (LNA-34a) following MI in adult mice Inhibition of miR-34a improves cardiac function in adult hearts post-MI.
miR-128 cardiacspecific miR-128 overexpression mice Overexpression of miR-128 impairs cardiac homeostasis, and inhibits neonatal cardiac regeneration. Suz12 (Huang et al. 2018)
cardiac-specific miR-128 knockout mice Inhibition of miR-128 promotes adult cardiac regeneration.
Let-7i-5p neonatal mouse CMs Let-7i-5p negatively regulates cardiomyocyte proliferation Ccnd2 and E2f2 (Hu et al. 2019)
Ad-let-7i-5p/ AAV9-anti-let-7i-5p was delivered to mice Overexpression of Let-7i-5p inhibits cardiomyocyte proliferation while inhibition of Let-7i-5p promotes cardiomyocyte proliferation.
miR-216a neonatal mouse CMs miR-216a negatively regulates cardiomyocyte proliferation Jak2 (Wang et al. 2019)