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Table 2 MicroRNAs promoting cardiomyocyte proliferation and cardiac regeneration

From: miRNA in cardiac development and regeneration

miRNA Experimental models Major findings Targets Ref.
miR-590-3p neonatal rat CMs, neonatal mouse CMs, postnatal rat (P7) CMs Overexpression of miR-590-3p increases CM proliferation. Homer1, Hopx,
Hippo pathway
(Eulalio et al. 2012; Torrini et al. 2019)
delivery of hsa-miR-590-3p complexed with a lipid transfection reagent into the heart of neonatal rats The left ventricle walls of the hearts appeared markedly thicker with increases CM proliferation.
delivery of AAV9-miR590 precursor miRNAs into the neonatal mice At 12 days after injection, the hearts were morphologically normal, but significantly enlarged.
delivery of AAV9-miR590 into the adult mice after infarction The infarct size was significantly reduced in mice.
miR-199a-3p neonatal rat CMs, neonatal mouse CMs, postnatal rat (P7) CMs Overexpression of miR-199a-3p increases CM proliferation. Homer1, Clic5, Cd151,
Hippo pathway
(Eulalio et al. 2012; Lesizza et al. 2017; Gabisonia et al. 2019; Tao et al. 2019; Torrini et al. 2019)
delivery of hsa-miR-199a-3p complexed with a lipid transfection reagent into the heart of neonatal rats The left ventricle walls of the hearts appeared markedly thicker with increases CM proliferation.
delivery of AAV9-miR-199a-3p precursor miRNAs into the neonatal mice At 12 days after injection, the hearts of these animals were morphologically normal, but significantly enlarged.
delivery of AAV9-miR-199a-3p into the adult mice after infarction The infarct size was significantly reduced in mice.
delivery of AAV9-miR 199a-1 pri-miRNA into the infarcted pig hearts The treated animals showed marked improvements in both global and regional contractility, increased muscle mass and reduced scar size. At longer follow-up, however, persistent and uncontrolled expression of the microRNA resulted in sudden arrhythmic death of most of the treated pigs.
miR-17-92 Cluster miR-17-92-cKO mice miR-17-92 is sufficient to induce cardiomyocyte proliferation in embryonic and postnatal hearts. Pten (Chen et al. 2013)
cardiac-specific overexpression miR-17-92 transgenic mice Overexpression of miR-17-92 induces cardiomyocyte proliferation in embryonic, neonatal and adult hearts. Overexpression of miR-17-92 in adult cardiomyocytes protects the heart from myocardial infarction-induced injury.
neonatal rat CMs miR-17-92 is sufficient to induce neonatal cardiomyocyte proliferation.
direct injection of miR-19a/19b mimics into the heart of a mouse model of MI miR-19a/19b overexpression enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury.
miRNA-204 neonatal and adult rat CMs Overexpression of miRNA-204 promotes cardiomyocyte proliferation Jarid2 (Liang et al. 2015)
cardiac-specific overexpression miRNA-204 transgenic mice Overexpression of miRNA-204 promotes cardiomyocyte proliferation throughout the embryonic and adult stages.
miR302–367 cluster cardiac-specific overexpression miR302–367 transgenic mice Overexpression of miR302–367 promotes cardiomyocyte proliferation in embryonic and postnatal hearts, and miR302–367 promotes adult cardiac regeneration after myocardial infarction. Hippo pathway (Tian et al. 2015)
delivery miR302–367 mimics into the adult mice Overexpression of miR302–367 promotes cardiac regeneration and improves function after injury.
miR-210 neonatal rat CMs miR-210 induces proliferation. Apc (Arif et al. 2017)
miR-210 overexpressing transgenic (210-TG) mice miR-210 overexpression promotes CM proliferation in adult mice post-ischemic injury.
miR-708 H9C2 cells, neonatal rat CMs, neonatal mouse CMs Overexpression of miR-708 promotes myocardium regeneration and heart function recovery. Mapk14 (Deng et al. 2017)
delivery miR-708 mimics to a mice model of cardiac hypertrophy
miR-1825 adult CMs Overexpression of miR-1825 induces robust proliferation. Hippo pathway (Pandey et al. 2017)
direct injection of AAV-miR-1825 into mice Overexpression of miR-1825 improves heart function.
miR-31a-5p neonatal rat CMs Overexpression of miR-31a-5p promotes cardiomyocyte proliferation. Rhobtb1 (Xiao et al. 2017)
neonatal rats were injected intraperitoneally with the miR-31a-5p antagomir Inhibition of miR-31a-5p decreases cardiomyocyte proliferation.
miR-294 neonatal and adult rat CMs Overexpression of miR-294 promotes cell cycle activity. Wee1 (Borden et al. 2019)
delivery of AAV-9-miR-294 to mice after MI Overexpression of miR-294 promotes cell cycle reentry and improves cardiac function.
miR-152 neonatal CMs Overexpression of miR-152 promotes neonatal cardiomyocyte proliferation. Cdkn1b and Dnmt1 (Wang et al. 2018)
miR-25 neonatal and adult CMs Inhibition of miR-25 reduces neonatal and adult cardiomyocyte proliferation. Bim and
FBXW7
(Qin et al. 2019; Wang et al. 2020)
hESC-CM miR-25 promotes hESC-CM proliferation.
Transgenic zebrafish Overexpressing miR-25 promotes cardiomyocyte proliferation in zebrafish.