title: Up-regulation of miR-138 inhibits hypoxia-induced cardiomyocyte apoptosis via down-regulating lipocalin-2 expression.
abstract: Hypoxia-induced cardiomyocyte apoptosis contributes significantly to the development of numerous cardiac diseases, such as ischemic heart disease, heart failure, etc. Promoting cell survival by inhibiting apoptosis is one of the available strategies to attenuate cardiac dysfunction caused by cardiomyocyte loss. Previous studies have been demonstrated that miR-138 and lipocalin-2 (Lcn2) play important roles in cardiomyocyte apoptosis and survival. We presently determined whether Lcn2 is a target gene of miR-138 involved in hypoxia-induced cardiomyocyte apoptosis. Firstly, mimics of miR-138 were transfected into HL-1 cells to investigate its effect on cell apoptosis. Using 3-(4,5-dimethyl-thiazol-2-y1) 2,5-diphenyl tetrazolium bromide (MTT) and Annexin V-FITC/PI flow cytometer assays, over-expression of miR-138 significantly enhanced the cell growth and significantly attenuated the cell apoptosis in hypoxic conditions. Dual-luciferase reporter gene and western blot results confirmed Lcn2 was a direct target of miR-138. Then, the recombinant plasmid, pcDNA3.1/Lcn2 was transfected into the HL-1 cells that over-expressed miR-138. We further observed that the over-expression of Lcn2 diminished the protection of miR-138 over-expression from hypoxia-induced cell survival and apoptosis. In conclusion, our study demonstrated that up-regulation of miR-138 inhibits the hypoxia-induced cardiomyocyte apoptosis via down-regulating the pro-apoptotic gene expression of Lcn2.
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Haowei
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Luo
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Wenshuai
authors.initials: W
authors.lastname: He
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xi
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lu
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Menghao
authors.initials: M
authors.lastname: Li
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Jichen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China guozhigang127@yeah.net.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000209:Acute-Phase Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002470:Cell Survival; D015536:Down-Regulation; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D000860:Hypoxia / Q000473:pathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology*; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; C583174:MIRN138 microRNA, mouse; D035683:MicroRNAs; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse; D008156:Luciferases
keywords: apoptosis; cardiomyocyte; hypoxia; lipocalin-2; miR-138