title: miR-153 regulates apoptosis and autophagy of cardiomyocytes by targeting Mcl-1.
abstract: MicroRNAs (miRs) are a class of important regulators, which are involved in the regulation of apoptosis. Oxidative stress‑induced apoptosis is the predominant factor accounting for cardiac ischemia‑reperfusion injury. miR‑153 has been previously shown to have an antitumor effect in cancer. However, whether miR‑153 is involved in oxidative stress‑induced apoptosis in the heart remains to be elucidated. To this end, the present study used reverse transcription‑quantitative polymerase chain reaction to detect miR-153 levels upon oxidative stress, and evaluated apoptosis, autophagy and expression of critical genes by western blotting. A luciferase assay was also used to confirm the potential target gene. In the present study, it was found that the expression of miR‑153 was significantly increased upon H2O2 stimulation, and the inhibition of endogenous miR‑153 decreased apoptosis. To further identify the mechanism underlying the pro‑apoptotic effect of miR‑153, the present study analyzed the 3'untranslated region of myeloid cell leukemia‑1 (Mcl‑1), and found that Mcl‑1 was potentially targeted by miR‑153. The forced expression of miR‑153 inhibited the expression of Mcl‑1 and luciferase activity, which was reversed by its antisense inhibitor. Furthermore, it was shown that the inhibition of miR‑153 induced autophagy during oxidative stress, and that its effects of autophagy induction and apoptosis inhibition were efficiently abrogated by Mcl‑1 small interfering RNA. In conclusion, the results of the present study elucidated a novel mechanism by which miR‑153 regulates the survival of cardimyocytes during oxidative stress through the modulation of apoptosis and autophagy. These effects may be mediated directly by targeting Mcl‑1. These finding revealed the potential clinical value of miR‑153 in the treatment of cardiovascular disease.
authors.affiliation: Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of ENT, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Dingcheng
authors.initials: D
authors.lastname: Xiang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D034622:RNA Interference; D051381:Rats
chemical_list: D020413:3' Untranslated Regions; C000606654:MIRN153 microRNA, rat; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D053148:Caspase 3; D053453:Caspase 9