lncRNA H19 Alleviated Myocardial I/RI via Suppressing miR-877-3p/Bcl-2-Mediated Mitochondrial Apoptosis

Xin Li; Shenjian Luo; Jifan Zhang; Yin Yuan; Wenmei Jiang; Haixia Zhu; Xin Ding; Linfeng Zhan; Hao Wu; Yilin Xie; Rui Song; Zhenwei Pan; Yanjie Lu

Molecular Therapy: Nucleic Acids (Sep 2019)

lncRNA H19 Alleviated Myocardial I/RI via Suppressing miR-877-3p/Bcl-2-Mediated Mitochondrial Apoptosis

Xin Li,
Shenjian Luo,
Jifan Zhang,
Yin Yuan,
Wenmei Jiang,
Haixia Zhu,
Xin Ding,
Linfeng Zhan,
Hao Wu,
Yilin Xie,
Rui Song,
Zhenwei Pan,
Yanjie Lu

Affiliations

Xin Li: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China; Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Shenjian Luo: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China; Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Jifan Zhang: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Yin Yuan: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Wenmei Jiang: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Haixia Zhu: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Xin Ding: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China; Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Linfeng Zhan: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Hao Wu: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Yilin Xie: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Rui Song: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
Zhenwei Pan: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China; Corresponding author: Zhenwei Pan, Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
Yanjie Lu: Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China; Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China; Corresponding author: Yanjie Lu, Department of Pharmacology, State Province Key Laboratories of Biomedicine–Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.

Journal volume & issue: Vol. 17
pp. 297 – 309

Abstract

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Ischemic cardiac disease is the leading cause of morbidity and mortality in the world. Despite the great efforts and progress in cardiac research, the current treatment of cardiac ischemia reperfusion injury (I/RI) is still far from being satisfactory. This study was performed to investigate the role of long non-coding RNA (lncRNA) H19 in regulating myocardial I/RI. We found that H19 expression was downregulated in the I/R hearts of mice and cardiomyocytes treated with H2O2. Overexpression of H19 alleviated myocardial I/RI of mice and cardiomyocyte injury induced by H2O2. We found that H19 functioned as a competing endogenous RNA of miR-877-3p, which decreased the expression of miR-877-3p through the base-pairing mechanism. In parallel, miR-877-3p was upregulated in H2O2-treated cardiomyocytes and mouse ischemia reperfusion (I/R) hearts. miR-877-3p exacerbated myocardial I/RI and cardiomyocyte apoptosis. We further established Bcl-2 as a downstream target of miR-877-3p. miR-877-3p inhibited the mRNA and protein expression of Bcl-2. Furthermore, H19 decreased the Bcl-2/Bax ratio at mRNA and protein levels, cytochrome c release, and activation of caspase-9 and caspase-3 in myocardial I/RI mice, which were canceled by miR-877-3p. In summary, the H19/miR-877-3p/Bcl-2 pathway is involved in regulation of mitochondrial apoptosis during myocardial I/RI, which provided new insight into molecular mechanisms underlying regulation of myocardial I/RI. Keywords: myocardial ischemia reperfusion injury, I/RI, lncRNA H19, miR-877-3p, Bcl-2, mitochondrial apoptosis

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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