Table 1.
Cardiomyocytes regulation: mechanistic insights on pro-proliferative miRNAs.
| miRNA | Model | Targets | Pathway | Effects | Mechanism(s) | Ref. |
|---|---|---|---|---|---|---|
| miR-10b | Hu | Lats1 | Hippo | ↓apoptosis | miR-10b blocks the expression of Lats1 and thereby inhibits the Hippo pathway | [45] |
| miR-17-92 | M; R | PTEN | Akt | ↑proliferation | miR-17-92 represses PTEN-inducing cardiomyocyte proliferation mediated by the AKt signaling pathway | [33] |
| miR19a/19b | M | PTEN | Akt | ↑proliferation | miR-19a/19b blocks the expression of PTEN inducing cardiomyocyte proliferation mediated by the AKt signaling | [34] |
| miR-21-5p | Hu | PDCD4/ PTEN |
Akt | ↑proliferation | miR-21-5p directly represses PCDN4 e PTEN-inducing cardiomyocyte proliferation mediated by the AKt signaling | [46] |
| miR-24 | R | p27 | Cell cycle | ↑proliferation | miR-24 promotes cells in G0/G1 phase into S phase by repressing p27 expression | [47] |
| miR-25 | Hu; Zb | FBXW7 | Cell cycle | ↑proliferation | miR-25 inhibits FBXW7, a cell-cycle regulatory factor that mediates the proteolysis of positive cell-cycle regulators | [48] |
| miR-101a | Hu | TGFBR1 | MAPK | ↑proliferation | miR-101a blocks the expression of TGFBR1 and thereby activates the MAPK signaling pathway | [49] |
| miR-145-5p | R | GIGYF1 | / | ↓apoptosis | miR-145-5p inhibits GIGYF1, a regulator of mRNA turnover, blocking translation and activating transcript decay | [50] |
| miR-152 | M | p27 | Hippo | / | The increase of miR-152 by the activation of YAP1 represses the expression of p27 | [51] |
| miR-199a-3p | R | CD151 | MAPK | ↑proliferation | miR-199a-3p inhibits the tetraspanin CD151, involved in several cellular process | [52] |
| miR-199a-3p | R | TAOK1 | Hippo | ↓apoptosis | miR-199a-3p represses Serine/threonine-protein kinase TAOK1 involved in the Hippo pathway | [53] |
| miR-199a-3p; -302d; -373; -590-3p; -1825 |
R | STK38L | Hippo | ↓apoptosis ↑proliferation |
They downregulate STK38L, a direct targeting on the 3’UTR of the related mRNA has not been identified | [53] |
| miR-200a-3p | Hu; M | PDCD4 | Akt | ↑proliferation | miR-200a-3p represses PCDN4 activating AKt signaling | [54] |
| miR-204 | R | Jarid2 | / | ↑proliferation | miR-204 downregulates Jarid2, a non-catalytic member of the polycomb repressive complex 2 | [42] |
| miR-210 | M | APC/β-catenin | WNT | ↑proliferation | miR-210 represses the cell cycle inhibitor APC, involved in the WNT pathway | [55] |
| miR-221-3p | R | PTEN | Akt | ↑proliferation | It enhances Akt kinase activity by inhibiting PTEN | [35] |
| miR-294 | M | Wee1 | Cell cycle | / | miR-294 inhibits Wee1, increasing the activity of the cyclin B1/CDK1 | [56] |
| miR-301a | M; R | PTEN | Akt | ↑proliferation | PTEN is a direct target of miR-301a in regulating cardiomyocyte proliferation | [57] |
| miR-302d; -373; -590-3p |
Hu | LATS2 | Hippo | ↓apoptosis ↑proliferation |
miR-302d, miR-373 and miR590-3p target LATS2, inhibiting the Hippo pathway | [58] [53] |
| miR-324 | Hu | SOCS3 | NFkB | ↑proliferation ↓apoptosis |
miR-32a represses SOCS3, activating the NFkB pathway | [38] |
| miR-362-3p | R | TP53INP2 | SDF1/ CXCR4 |
↑proliferation ↓apoptosis |
miR-362-3p downregulates TP53INP2, activating at the same time the SDF-1/CXCR4 pathway | [59] |
| miR-374 | M | DTNA | Notch | ↑viability ↓apoptosis |
miR-374 inhibits DTNA and the Notch1 axis | [60] |
| miR-410; -495 | M; R | Cited2 | Cell cycle | ↑proliferation | miR-410 and miR-495 downregulate the transcriptional coactivator Cited2 | [61] |
| miR-410-3p | Hu | TRAF5 | NFkB | ↓apoptosis | miR-410-3p protects CMs from apoptosis by repressing TRAF5 expression | [62] |
| miR-496 | R | HOOK3 | Akt | ↓apoptosis ↑proliferation |
miR-496 binds to Hook3 to inhibit the activation of PI3K/Akt/mTOR signalling pathway | [63] |
| miR-499 | M; R | SOX6 | Cell cycle | ↑proliferation ↓apoptosis |
miR-499 promotes cell proliferation and inhibits apoptosis in the late stage of cardiac differentiation targeting SOX6 and leading to activation of cyclin D1 | [29] |
| miR-708 | M; R | MAPK14 | MAPK | ↑proliferation | miR-708 inhibits the expression of MAPK14, which arrests the cell cycle in CMs | [64] |
| miR-877-3p | M | GADD45g | Cell cycle | ↑proliferation | LED-Red irradiation increases miR-877-3p expression promoting proliferation of neonatal CMs via GADD45g | [65] |
| miR-1180 | R | NKIRAS2 | NFkB | ↑proliferation ↑viability ↓apoptosis |
miR-1180 represses the NF-κB inhibitor interacting with Ras-like 2 (NKIRA2), activating the NFkB pathway | [39] |
Abbreviations: Hu: human; M: murine; R: rat; Zb: zebrafish.; ↑: upregulation/increase; ↓: downregulation/decrease.