Jiayong Zheng1, Bangtian Peng2, Yanwei Zhang1, Feng Ai1, Xiaosong Hu1. 1. Department of Children's Heart Center, Henan Provincial People's Hospital, Fuwai Central China Cardiovascular Hospital, No. 1 Fuwai Avenue, Zhengzhou 450000, China. 2. Department of Children's Heart Center, Henan Provincial People's Hospital, Fuwai Central China Cardiovascular Hospital, No. 1 Fuwai Avenue, Zhengzhou 450000, China. Electronic address: pbangtian@163.com.
Abstract
AIMS: Aberrantly expressed miRNAs are demonstrated to be involved in the development of congenital heart disease (CHD). miR-9 was proposed to be upregulated in cardiac tissues from CHD cases. However, the role of miR-9 in hypoxia-induced cardiomyocytes and the potential mechanism are far from being addressed. MAIN METHODS: qRT-PCR and western blot analysis were performed to detect miR-9 and Yes-associated protein 1 (Yap1) expressions in hypoxic H9c2 cells. CCK-8, flow cytometry analysis, caspase-3/7 activity assay were applied to evaluate cell proliferation, apoptosis, and caspase-3/7 activity, respectively. The interaction between miR-9 and Yap1 was explored by luciferase reporter assay, qRT-PCR and western blot. KEY FINDINGS: miR-9 was upregulated and Yap1 was downregulated in H9c2 cells in response to hypoxia in a time-dependent manner. Knockdown of miR-9 promoted cell proliferation, and inhibited apoptosis and caspase-3/7 activity in hypoxic H9c2 cells, while miR-9 overexpression exerted the opposite effects on hypoxic H9c2 cells. In addition, Yap1 was a direct target of miR-9 in H9c2 cells. Yap1 knockdown suppressed cell proliferation and promoted apoptosis in hypoxia-exposed H9c2 cells. Yap1 knockdown attenuated the effect of anti-miR-9 on cell proliferation and apoptosis in hypoxia-exposed H9c2 cells. SIGNIFICANCE: miR-9 knockdown inhibited hypoxia-induced cardiomyocyte apoptosis by targeting Yap1. Our study provided a novel insight into the mechanism of the adaptation of cardiomyocytes to chronic hypoxia.
AIMS: Aberrantly expressed miRNAs are demonstrated to be involved in the development of congenital heart disease (CHD). miR-9 was proposed to be upregulated in cardiac tissues from CHD cases. However, the role of miR-9 in hypoxia-induced cardiomyocytes and the potential mechanism are far from being addressed. MAIN METHODS: qRT-PCR and western blot analysis were performed to detect miR-9 and Yes-associated protein 1 (Yap1) expressions in hypoxic H9c2 cells. CCK-8, flow cytometry analysis, caspase-3/7 activity assay were applied to evaluate cell proliferation, apoptosis, and caspase-3/7 activity, respectively. The interaction between miR-9 and Yap1 was explored by luciferase reporter assay, qRT-PCR and western blot. KEY FINDINGS: miR-9 was upregulated and Yap1 was downregulated in H9c2 cells in response to hypoxia in a time-dependent manner. Knockdown of miR-9 promoted cell proliferation, and inhibited apoptosis and caspase-3/7 activity in hypoxic H9c2 cells, while miR-9 overexpression exerted the opposite effects on hypoxic H9c2 cells. In addition, Yap1 was a direct target of miR-9 in H9c2 cells. Yap1 knockdown suppressed cell proliferation and promoted apoptosis in hypoxia-exposed H9c2 cells. Yap1 knockdown attenuated the effect of anti-miR-9 on cell proliferation and apoptosis in hypoxia-exposed H9c2 cells. SIGNIFICANCE: miR-9 knockdown inhibited hypoxia-induced cardiomyocyte apoptosis by targeting Yap1. Our study provided a novel insight into the mechanism of the adaptation of cardiomyocytes to chronic hypoxia.
Authors: Kele Qin; Xiaohui Xie; Weijie Tang; Danni Yang; Jun Peng; Jianjun Guo; Jinfu Yang; Chengming Fan Journal: Front Cardiovasc Med Date: 2022-08-18