miRNA in cardiac development and regeneration

Ouyang, Zhaohui; Wei, Ke

doi:10.1186/s13619-021-00077-5

Cell Regeneration

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)
miRNA-204	cardiac-specific overexpression miRNA-204 transgenic mice	Overexpression of miRNA-204 promotes cardiomyocyte proliferation throughout the embryonic and adult stages.	Jarid2	(Liang et al. 2015)
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)
miR302–367 cluster	delivery miR302–367 mimics into the adult mice	Overexpression of miR302–367 promotes cardiac regeneration and improves function after injury.	Hippo pathway	(Tian et al. 2015)
miR-210	neonatal rat CMs	miR-210 induces proliferation.	Apc	(Arif et al. 2017)
miR-210	miR-210 overexpressing transgenic (210-TG) mice	miR-210 overexpression promotes CM proliferation in adult mice post-ischemic injury.	Apc	(Arif et al. 2017)
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)
miR-708	delivery miR-708 mimics to a mice model of cardiac hypertrophy		Mapk14	(Deng et al. 2017)
miR-1825	adult CMs	Overexpression of miR-1825 induces robust proliferation.	Hippo pathway	(Pandey et al. 2017)
miR-1825	direct injection of AAV-miR-1825 into mice	Overexpression of miR-1825 improves heart function.	Hippo pathway	(Pandey et al. 2017)
miR-31a-5p	neonatal rat CMs	Overexpression of miR-31a-5p promotes cardiomyocyte proliferation.	Rhobtb1	(Xiao et al. 2017)
miR-31a-5p	neonatal rats were injected intraperitoneally with the miR-31a-5p antagomir	Inhibition of miR-31a-5p decreases cardiomyocyte proliferation.	Rhobtb1	(Xiao et al. 2017)
miR-294	neonatal and adult rat CMs	Overexpression of miR-294 promotes cell cycle activity.	Wee1	(Borden et al. 2019)
miR-294	delivery of AAV-9-miR-294 to mice after MI	Overexpression of miR-294 promotes cell cycle reentry and improves cardiac function.	Wee1	(Borden et al. 2019)
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.

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