title: MicroRNA-146b inhibition augments hypoxia-induced cardiomyocyte apoptosis.
abstract: MicroRNAs (miRs) regulate a number of physiological and pathological processes, including myocardial chronic hypoxia. Previous studies revealed that the expression of miR-146b is increased in vitro and in vivo following the induction of hypoxia. In the present study, the role of miR‑146b in hypoxic cardiomyocytes, and the mechanisms underlying its activity, were investigated. The expression of miR‑146b was measured in tissue samples from patients with congenital heart disease by reverse transcription‑quantitative polymerase chain reaction. The rat H9c2 cardiomyocyte cell line was transfected with an miR‑146b inhibitor or the experimental controls, and the cells were maintained under hypoxic conditions for 72 h. The expression of miR‑146b increased following the induction of hypoxia. Transfection with the miR‑146b inhibitor enhanced the release of lactate dehydrogenase and increased hypoxia‑induced apoptosis, as determined by terminal deoxynucleotidyl transferase dUTP nick‑end labeling, Hoechst 33258 staining, JC‑1 assay (measuring mitochondrial membrane permeability) and annexin V/propidium iodide analysis. A decreased expression of Bcl‑2 was observed, whereas the expression levels of cleaved‑caspase 3 and Bax were increased. Western blot analysis and a dual luciferase reporter assay confirmed that ribonuclease L is a direct target of miR‑146b. Furthermore, inhibition of miR-146b increased the activation of nuclear factor-κB and signal transducer and activator of transcription 3. In conclusion, the inhibition of miR‑146b may increase hypoxia-induced cardiomyocyte apoptosis.
authors.affiliation: Department of Cardiovascular Surgery, PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: He
authors.affiliation: Department of Cardiovascular Surgery, PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Ze-Zhou
authors.initials: ZZ
authors.lastname: Feng
authors.affiliation: Department of Cardiovascular Surgery, PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular Surgery, PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Wei-Kun
authors.initials: WK
authors.lastname: Jia
authors.affiliation: Department of Cardiovascular Surgery, PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Cardiovascular Surgery, PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jian
authors.affiliation: Department of Cardiovascular Surgery, PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002460:Cell Line; D002478:Cells, Cultured; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007223:Infant; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D014162:Transfection; D015854:Up-Regulation
chemical_list: C542542:MIRN146 microRNA, human; C554180:MIRN146 microRNA, rat; D035683:MicroRNAs