Table 2.

Cardiomyocytes regulation: mechanistic insights on anti-proliferative/pro-apoptotic miRNAs.

miRNA	Model	Targets	Pathway	Effects	Mechanism(s)	Ref.
Let-71-5p	M	E2F2–CCND2	Cell cycle	↓proliferation	Let-7i-5p downregulates the expression of E2F2 and CCND2 and further represses CM proliferation	[66]
miR-1	M	CCND1	Cell cycle	↓proliferation	It directly suppresses the cell-cycle regulator CCND1	[67]
miR-1	R	NOTCH3	Notch	↑apoptosis ↓proliferation ↓autophagy	miR-1 suppresses NOTCH3 thereby negatively regulating the Notch pathway	[68]
miR-9	R	YAP1	Hippo	↑apoptosis	miR-9 promotes hypoxia-induced cardiomyocyte apoptosis by targeting Yap1	[69]
miR-26a	R, Zb	Ezh2	/	↓proliferation	miR-26a targets activators of the cell cycle and Ezh2, a component of PRC2, with repressive functions on negative regulators of the cell cycle	[43]
miR29a	R	CCND2	Cell cycle	↓proliferation	miE29a inhibits proliferation by acting on cyclin D2	[70]
miR-29a; -30a; -141	R	CCNA2–CDK6	Cell cycle	↓proliferation	miR-29a, miR-30a and miR-141 reduce expression of Cyclin A2, reducing cell proliferation	[71]
miR29b-3p	R; Zb	NOTCH2	Notch	↓proliferation	miR29b-3p inhibits CMs proliferation by targeting NOTCH2	[72]
miR-33a-5p	Hu	NOMO1	Nodal	↓proliferation ↑apoptosis ↓differentiation	miR-33a-5p targets NOMO1, a component of a protein complex involved in Nodal signaling leading to apoptosis	[41]
miR-34a	M; R	Bcl2, Sirt1, CCND1	/	↓proliferation ↑apoptosis	miR-34a directly regulated cell cycle and death via modulation of its targets such as Bcl2, Cyclin D1, and Sirt1	[73]
miR-128	R	SUZ12	Cell cycle	↓proliferation	miR-128 downregulates SUZ12, which cannot suppress p27 expression and activate the positive cell cycle regulators Cyclin E and CDK2	[74]
miR-133a	M	CCND2 SRF	Cell cycle Akt	↓proliferation	miR-133 functions as an inhibitor of cardiomyocyte proliferation, targeting cyclin D2 and SRF.	[75]
miR-143-3p	M	YAP–Ctnnd1	Hippo	↑apoptosis	miR-143-3p inhibited the mitosis of CMs, targeting YAP and Ctnnd1	[76]
miR-144	R	TBX1	Jak2/Stat1	↑apoptosis	miR-144 leads to proliferation via TBX1/JAK2/STAT1 axis	[77]
miR-195	M	Chek1	Cell cycle	↓proliferation	miR-195 regulates the expression of many cell cycle genes, including Chek1	[30]
miR-208a	R	PI3K	Akt	↑apoptosis ↑autophagy	miR-208a inhibits the PI3K/AKT pathway	[36]
miR-322; -503	M	IGF2 FGF9	Akt	↓proliferation	They suppress FGF9 and IGF2, disrupting epicardial signaling and impairing myocardial growth	[44]
miR-423	R	MYBL2	WNT	↑apoptosis	miR-423 silences MYBL2 with suppression of wnt/β-	[78]
miR-484	R	YAP1	Hippo	↑apoptosis ↑inflammation	Catenin signaling pathway	[79]
miR-489	R	SPIN1	Akt	↑apoptosis	It directly targets Yap1mRNA to inhibit cell viability	[37]
miR-873	R	GLI1	Hedgehog	↓proliferation	It inhibits SPIN1 thereby inactivating the Akt pathway	[80]

Abbreviations: Hu: human; M: murine; R: rat; Zb: zebrafish.; ↑: upregulation/increase; ↓: downregulation/decrease.