Effects of miR‐181a targeting XIAP gene on apoptosis of cardiomyocytes induced by hypoxia/reoxygenation and its mechanism. Issue 5 (28th November 2018)

• Record Type: Journal Article
• Authors: Hao, Peiyuan; Cao, Xueming; Zhu, Zhongyu; Gao, Chuanyu; Chen, Yan; Qi, Datun
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 5(2019)
• Page Start: 8385
• Page End: 8392
• Publication Date: 2018-11-28
• Subjects: cardiomyocyte apoptosis -- hypoxia/reoxygenation -- miR‐181a -- XIAP; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28123
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: To investigate the effect of miR‐181a targeting XIAP gene on the apoptosis of cardiomyocytes induced by hypoxia/reoxygenation (H/R) and its mechanism. The primary cultured cardiomyocytes were treated with hypoxia for 3 hours and reoxygenation for 4 hours to construct H/R cell model. The expression of miR‐181a and XIAP messenger RNA in cardiomyocytes was detected by reverse‐transcription polymerase chain reaction, and the expression of XIAP protein in cardiomyocytes was detected by Western blot analysis. H/R cardiomyocytes with low expression of miR‐181a and overexpression of XIAP were constructed, and the effects of low expression of miR‐181a and upregulation of XIAP on cardiomyocyte apoptosis were detected by flow cytometry. A dual luciferase reporter assay was used to detect the target relationship between miR‐181a and XIAP. Further, H/R myocardial cells with low XIAP expression were constructed to observe the effect of downregulation of XIAP expression on apoptosis of myocardial cells with low expression of microarray‐181a. The expression of apoptosis‐related proteins Bax and Bcl‐2 in myocardial cells was detected by Western blot analysis. After H/R treatment, the expression of microRNAs‐181a was high but that of XIAP was low. The apoptosis of cardiomyocytes could be inhibited by both the low expression of miR‐181a and the upregulation of XIAP. The results of dual luciferase reporter gene showed that XIAP was a potential target gene for miR‐181a. The inhibitory effect of low expression of miR‐181a on myocardial apoptosis could be reversed and the inhibitory effect of low expression of miR‐181a on Bax protein expression and the promotion of Bcl‐2 protein expression could be reversed by the downregulation of XIAP. MiR‐181a can inhibit the apoptosis of hypoxic‐reoxygenated cardiomyocytes by targeting XIAP to downregulate Bax and upregulate Bcl expression. Abstract : MiR‐181a is highly expressed in cardiomyocytes under hypoxia/reoxygenation (H/R) conditions. Downregulation of its expression can inhibit cardiomyocyte apoptosis by targeting XIAP to downregulate Bax and upregulatie Bcl expression. This provides new data for the role of miR‐181a in H/R‐induced myocardial injury, and provides a new basis for the treatment of myocardial ischemia‐reperfusion injury with miR‐181a as a target. In this study, only in vitro primary cells were tested with certain limitations. It will be further verified from in vivo rat experiments.