Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN

• Published in: International journal of medical sciences Vol. 17; no. 10; pp. 1415 - 1427
• Main Authors: Li, Zhiqiang, Li, Hongqiang, Liu, Baoxin, Luo, Jiachen, Qin, Xiaoming, Gong, Mengmeng, Shi, Beibei, Wei, Yidong
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2020; Ivyspring International Publisher
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Binding sites; Cell Line; Cell Survival - drug effects; Cell Survival - genetics; DNA damage; DNA Damage - drug effects; DNA Damage - genetics; Doxorubicin - pharmacology; Flow Cytometry; Gene expression; Heart failure; Laboratory animals; Manufacturers; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Rats; Reactive Oxygen Species - metabolism; Reagents; Research Paper; Beijing China; United States > US; China; Japan; PTEN; doxorubicin-induced cardiotoxicity; miR-25; H9c2 cells
• ISSN: 1449-1907; 1449-1907
• DOI: 10.7150/ijms.41980

: Doxorubicin (DOX) is one of the widely used anti-cancer drugs, whereas it can induce irreversible cardiac injury in a dose-dependent manner which limits its utility in clinic. Our study aimed to investigate the relationship between miR-25 and DOX-induced cardiac injury and its underlying mechanism. : Mice and H9c2 cells were exposed to DOX. The overexpressed or knockdown of miR-25 in H9c2 cells was achieved by miR-25 mimic or inhibitor and the efficiency of transfection was identified by qRT-PCR or Western blotting. Cell viability, apoptotic cell rate, and levels of apoptosis-related proteins were determined by CCK-8, flow cytometry, and Western blotting, respectively. Furthermore, Western blotting and immunofluorescence staining (IF) were performed to assess the expression levels of reactive oxygen species and degree of DNA damage. : As a result, DOX significantly upregulated miR-25 expression in mice and H9c2 cells and reduced cell viability and increased cell apoptosis and . miR-25 overexpression expedited cell injury induced by DOX in H9c2 cells demonstrated by the increased cell apoptosis and reactive oxygen species (ROS) production, whereas miR-25 inhibition attenuated the cell injury. Furthermore, miR-25 negatively controlled the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Intervention the expression of PTEN using si-PTEN reversed the beneficial effects of miR-25 inhibition on DOX-injured H9c2 cells. : In conclusion, this study demonstrated that miR-25 is involved in DOX-induced cell damage through the regulation of PTEN expression.