2023, Vol. 27 ›› Issue (11): 1750-1757

piRNA-5938 can regulate cardiomyocyte apoptosis and mitochondrial fission

Wu Xiaolei, Han Yu, Li Jialei, Wang Shuang, Cao Jimin, Sun Teng   

Abstract: BACKGROUND: Cardiomyocyte apoptosis plays a critical role in ischemia/reperfusion injury. Recent studies have shown that PIWI-Interacting RNA (piRNA), a reproductive system regulator, participates in the pathogenesis of cardiac disorder. However, the role of piRNA in cardiomyocyte apoptosis has not been clarified; especially the mitochondria-dependent pathway involved is poorly understood.
OBJECTIVE: To study the role and molecular mechanism of piRNA-5938 in cardiomyocyte apoptosis and mitochondrial fission.
METHODS: The abundance of piRNA in normal and ischemic/reperfusion hearts of mice and rats was detected by deep sequencing, and the results were verified by real-time fluorescence quantitative PCR. Cardiac apoptosis was induced by hydrogen peroxide or anoxia/reoxygenation, in which the expression level of piRNA-5938 was detected by real-time fluorescence quantitative PCR. piRNA-5938 antagomir was synthesized and transfected into cardiomyocytes and then the cells were treated with hydrogen peroxide. Apoptosis was detected by TUNEL and mitochondrial division was evaluated by MitoTracker. RNAhybrid software was used to predict microRNAs that interact with piRNA-5938.
RESULTS AND CONCLUSION: Compared with the sham group, the expression levels of 422 piRNAs were changed in the mouse ischemic/reperfusion heart, of which 289 were up-regulated and 133 were down-regulated, and piRNA-5938 expression increased significantly (P < 0.01). The expression level of piRNA-5938 was significantly up-regulated after cardiomyocyte apoptosis induced by H2O2 in a concentration-dependent manner (P < 0.05). piRNA-5938 was significantly increased after anoxia/reoxygenation-induced cardiomyocyte apoptosis (P < 0.01). Compared with the negative control group, knockdown of piRNA-5938 significantly reduced the apoptosis rate of cardiomyocytes induced by hydrogen peroxide (P < 0.05). The mitochondrial fission induced by hydrogen peroxide was significantly inhibited by the knockdown of piRNA-5938 (P < 0.05). piRNA-5938 was highly conserved in complementation with mitochondrial fission regulators mir-324 and Mir-668. To conclude, piRNA-5938 regulates cardiomyocyte apoptosis and mitochondrial fission, which probably functions through targeting mir-324 or mir-668.
Key words: piRNA-5938, ischemia/reperfusion injury, cardiomyocyte apoptosis, mitochondrial fission, miR-324, miR-668, hydrogen peroxide, anoxia/reoxygenation