Overexpression of miR-654-3p may inhibit myocardial hypertrophy via HDAC2

Myocardial hypertrophy (MH) is one of the key features of pathological cardiac hypertrophy (CH). MicroRNAs (miRNAs) possess significant regulatory potential in MH. This study aims to investigate the potential function and molecular mechanisms of miR-654-3p in MH.

An in vitro MH model was established by treating AC16 cells with 200 nM Ang II. Changes in miR-654-3p and markers of MH and myocardial fibrosis (MF) were assessed using RT-qPCR. Changes in oxidative stress (OS) markers were evaluated using ELISA. The binding capacity of miR-654-3p to HDAC2 was validated via dual luciferase assays and RIP experiments. The functional relationship was verified through rescue experiments.

Following Ang II stimulation, miR-654-3p was reduced in AC16 cells, whilst HDAC2 levels increased. Concurrently, mRNA levels of MH markers rose, MDA levels increased, and SOD activity decreased. Overexpression of miR-654-3p improved these parameters, whereas inhibition of miR-654-3p exacerbated the damage. Rescue experiments demonstrated that the addition of oe-HDAC2 could reverse the anti-hypertrophic, anti-fibrotic, and anti-OS effects mediated by the miR-654-3p mimic.

Overexpression of miR-654-3p alleviates MH and OS by directly targeting and downregulating HDAC2. The miR-654-3p/HDAC2 axis may represent a potential regulatory mechanism for MH.