Inhibition of miR-182-5p attenuates ROS and protects against myocardial ischemia-reperfusion injury by targeting STK17A

• Published in: Cell cycle (Georgetown, Tex.) Vol. 21; no. 15; pp. 1639 - 1650
• Main Authors: Li, Xia, Jin, Yalei
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03.08.2022
• Subjects: Animals; apoptosis; Apoptosis - genetics; Apoptosis Regulatory Proteins - genetics; Catalase - genetics; Catalase - metabolism; MicroRNAs - metabolism; MiR-182-5p; Myocardial Infarction - genetics; Myocardial Infarction - metabolism; myocardial ischemia-reperfusion injury; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - metabolism; Myocytes, Cardiac - metabolism; Protein Serine-Threonine Kinases - genetics; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Research Paper; ROS; STK17A; apoptosis; myocardial ischemia-reperfusion injury; STK17A; ROS; MiR-182-5p
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2022.2060640

Reperfusion therapy for acute myocardial infarction inevitably leads to ischemia-reperfusion (I/R) injury. A number of miRNAs are reported to be involved in I/R injury. This study aims to investigate the role and underlying mechanism of miR-182-5p in I/R injury. An in vivo model of I/R-induced rat myocardial injury and an in vitro model of H/R H9c2 cells were established to investigate the role and mechanism of miR-182-5p in I/R injury. The myocardial infarct size was determined by TTC staining. The serum CK-MB level was determined by ELISA kit. The miR-182-5p inhibitors or mimics were used to down-regulate or up-regulate its expression. The apoptosis and ROS were detected by flow cytometry. The expression of the proteins was detected by western blot. The binding of STK17A and miR-182-5p was validated by dual-luciferase reporter assay. The miR-182-5p was confirmed to be highly expressed in I/R injury rats and H/R H9c2 cells. Inhibition of miR-182-5p significantly reduced the infarct size and decreased the serum CK-MB level of I/R rats, and significantly reduced the ROS level but increased the level of MnSOD and catalase. While, an opposite effect was observed in the miR-182-5p mimics group. Furthermore, our results suggested that miR-182-5p targeted STK17A, and TK17A knockdown significantly increased the apoptotic rate and ROS level. The inhibitory effect of miR-182-5p inhibitors on apoptotic rate, ROS, MnSOD, and catalase levels were abrogated by siSTK17A. These results indicate that miR-182-5p regulates the apoptosis and ROS and protects against myocardial I/R injury by targeting STK17A.