MicroRNA‑133b alleviates doxorubicin‑induced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2.

ABSTRACT: Doxorubicin is one of the most important chemotherapeutic drugs for the treatment of malignant tumors, but the cardiotoxicity of doxorubicin severely limits its clinical application. Increasing numbers of microRNAs (miRNAs/miRs) have been found to be dysregulated in doxorubicin‑treated cardiomyocytes or animal hearts. The current study aimed to investigate the role of miR‑133b in doxorubicin‑induced cardiomyocyte injury. Doxorubicin was used to treat HL‑1 cardiomyocytes to mimic cardiomyocyte injury in vitro. A mouse model of cardiac injury was generated by chronic intraperitoneal injections of doxorubicin. Masson's trichrome staining was performed on cardiac tissues to reveal cardiac fibrosis. Bioinformatics analysis and luciferase reporter assays were applied to explore the downstream targets of miR‑133b. Flow cytometry and western blotting were conducted to detect cardiomyocyte apoptosis. Protein expression levels of collagen I, III and IV, and fibronectin were detected to reveal extracellular matrix deposition. The results revealed that doxorubicin decreased miR‑133b expression in the treated HL‑1 cardiomyocytes and mouse hearts. Overexpression of miR‑133b restrained cardiomyocyte apoptosis, inhibited collagen accumulation and alleviated cardiac fibrosis in vivo. Mechanistically, polypyrimidine tract binding protein 1 (PTBP1) and transgelin 2 (TAGLN2) were confirmed to bind to miR‑133b after prediction and screening. Moreover, miR‑133b negatively regulated the protein expression levels of PTBP1 and TAGLN2. Finally, overexpression of PTBP1 or TAGLN2 reversed the effects of miR‑133b on apoptosis and collagen accumulation. Thus, the current results indicated that miR‑133b alleviated doxorubicin‑induced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2, implying that miR‑133b may be a potential biomarker for doxorubicin‑induced cardiac injury.

SUBMITTER: Li Z 

PROVIDER: S-EPMC8128419 | biostudies-literature |

REPOSITORIES: biostudies-literature