title: Inhibition of miR-363 protects cardiomyocytes against hypoxia-induced apoptosis through regulation of Notch signaling.
abstract: Cardiomyocyte apoptosis contributes to the pathological process of ischemic heart diseases, such as myocardial infarction. Emerging evidence suggests that microRNAs (miRNAs) play critical roles in the pathological process of myocardial infarction by regulating cardiomyocyte apoptosis. Previous studies have reported that miR-363 is an apoptosis-related miRNA. However, whether miR-363 is involved in regulating cardiomyocyte apoptosis remains unclear. This study aimed to investigate the potential role of miR-363 in the regulation of hypoxia-induced cardiomyocyte apoptosis. We found that miR-363 expression was significantly increased in hypoxic cardiomyocytes and that inhibition of miR-363 effectively protected cardiomyocytes against hypoxia-induced apoptosis. Bioinformatics analysis predicted that Notch1 is a potential target gene of miR-363. This finding was validated by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. miR-363 inhibition significantly promoted the activation of Notch signaling in hypoxic cardiomyocytes. However, knockdown of Notch1 markedly reversed the protective effects induced by miR-363 inhibition. Furthermore, blocking the Notch signaling also significantly abrogated the protective effects of miR-363 inhibition. Overall, these findings suggest that inhibition of miR-363 protects cardiomyocytes against hypoxia-induced apoptosis through promotion of Notch1 expression and activation of Notch signaling. Our study provides a novel understanding of the molecular basis of hypoxia-induced cardiomyocyte apoptosis and suggests a potential therapeutic target for myocardial infarction.
authors.affiliation: Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou 730000, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Cardiovascular Medicine, First Hospital of Xi'an, Xi'an 710002, China; The College of Life Science, Northwest University, Xi'an 710069, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Cardiology, Affiliated Hospital, Yan'an University, Yan'an 716000, China.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Cardiology, Affiliated Hospital, Yan'an University, Yan'an 716000, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Affiliated Hospital, Yan'an University, Yan'an 716000, China.
authors.forename: Chuanjie
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Affiliated Hospital, Yan'an University, Yan'an 716000, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics, Affiliated Hospital, Yan'an University, No. 43 North Street, Yan'an 716000, China. Electronic address: huali_ya@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: The College of Life Science, Northwest University, Xi'an 710069, China; Department of Cardiology, Affiliated Hospital, Yan'an University, Yan'an 716000, China. Electronic address: yanbin_songyb@163.com.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D035683:MicroRNAs; D020011:Protective Agents; D051881:Receptor, Notch1
keywords: Apoptosis; Cardiomyocyte; Hypoxia; Notch1; miR-363