Upregulation of miR‐144‐3p alleviates Doxorubicin‐induced heart failure and cardiomyocytes apoptosis via SOCS2/PI3K/AKT axis

Abstract MicroRNAs (miRs) are implicated in heart failure (HF). Thereby, we aim to uncover the role of miR‐144‐3p in HF. Doxorubicin (Dox)‐induced HF model was constructed in rats and cardiomyocytes H9C2, and the cardiac function was determined using ultrasound cardiogram. Morphology of cardiac tissue was observed using hematoxylin–eosin (H&E) staining. The viability and apoptosis of Dox‐treated and transfected cardiomyocytes were determined using Cell Counting Kit‐8 (CCK‐8) assay and flow cytometry. Relative expressions of the HF‐associated miRs (including miR‐144‐3p), suppressor of cytokine signaling 2 (SOCS2), apoptosis‐ and phosphoinositide 3‐kinase (PI3K)/AKT pathway‐related factors (B‐cell lymphoma 2, Bcl‐2; Bcl‐2 associated X protein, Bax; cleaved [C] capsase‐3; phosphoinositide 3‐kinase, PI3K; phosphorylated‐PI3K, p‐PI3K; p‐AKT; AKT) were measured with quantitative real‐time polymerase chain reaction or Western blot. Target gene of miR‐144‐3p was predicted by Starbase and TargetScan and confirmed with dual‐luciferase reporter assay. Dox caused rat cardiac dysfunction, aggravated cardiac injury, decreased cardiomyocytes viability, and the expression of miR‐144‐3p, Bcl‐2, and phosphorylation of both PI3K and AKT yet the upregulated those of Bax and C caspase‐3, which was reversed by upregulating miR‐144‐3p, whereas downregulating miR‐144‐3p did oppositely. SOCS2 was the target gene of miR‐144‐3p, Dox promoted SOCS2 expression, which was reversed by upregulating miR‐144‐3p, while downregulating miR‐144‐3p did conversely. In addition, silencing SOCS2 reversed the effects of miR‐144‐3p downregulation in Dox‐treated cardiomyocytes. Upregulating miR‐144‐3p alleviated Dox‐induced cardiac dysfunction and cell apoptosis via targeting SOCS2, providing a novel evidence of miR‐144‐3p in HF.