Circ_0068655 Promotes Cardiomyocyte Apoptosis via miR-498/PAWR Axis
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Online ISSN 2212-5469
ORIGINAL ARTICLE
Circ_0068655 Promotes Cardiomyocyte Apoptosis via miR-498/ PAWR Axis Qiaoying Chai1,2 • Mingqi Zheng2 • Le Wang2 • Mei Wei2 • Yajuan Yin2 Fangfang Ma2 • Xinping Li1 • Haijun Zhang1 • Gang Liu2
•
Received: 18 March 2020 / Revised: 29 April 2020 / Accepted: 2 May 2020 Ó The Korean Tissue Engineering and Regenerative Medicine Society 2020
Abstract BACKGROUND: The cardiomyocyte apoptosis is considered as one of major contributions to cardiac remodeling after myocardial infarction (MI). Numerous studies find that circular RNAs (circRNAs) play pivotal roles in a variety of biological functions. However, the role of circ_0068655 in MI and human induced pluripotent stem-derived cardiomyocytes (HCMs) remains unknown. METHODS: The expression of circ_0068655, miR-498, and PRKC apoptosis WT1 regulator (PAWR) in human MI heart tissues and hypoxia subjected HCMs was evaluated with qRT-PCR and Western blot. The effects of circ_0068655 on hypoxia-induced apoptotic death and cell migration in HCMs were evaluated with qRT-PCR, cell viability, cell death ELISA (POD), and Caspase-3 activity assay, and Trans-well assay, respectively. Furthermore, luciferase assay, qRT-PCR, biotin-labeled miRNA pulldown assay, and Western blot were employed in the functional studies. RESULTS: We found that the expression of circ_0068655 and PAWR was enhanced in MI patients and hypoxia subjected HCMs; by contrast, the expression of miR-498 decreased. Inhibited expression of circ_0068655 in HMCs counteracted hypoxia-induced apoptotic death and impaired cell migration, in sharp contrast to circ_0068655 knockdown. We identified that circ_0068655 sponged an endogenous miR-498 to sequester and inhibit its activity, leading to the increased PAWR expression. CONCLUSIONS: Our findings reveal that the expression of circ_0068655 can promote cardiomyocyte apoptosis through the modulation of miR-498-PAWR axis in vitro, which highlights the diagnostic and therapeutic value of circ_0068655 in patients with MI. Keywords Circular RNA Myocardial infarction MiR-498 PAWR Cardiomyocyte apoptosis
1 Introduction
& Gang Liu [email protected] 1
Department of Cardiovasology, Han Dan First Hospital, No. 24, Congtai Road, Congtai District, Handan, Hebei 056001, China
2
Department of Cardiovasology, the First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang, Hebei 050031, China
Myocardial infarction (MI) is a common cardiac emergency with a sudden loss of blood or oxygen supply [1]. Cardiomyocyte apoptosis, hypertrophy, and a series of inflammatory and immune responses are associated with MI [2, 3, 4], leading to chronic heart failure and cardiac remodeling [5, 6]. Even though the management of MI has been improved over the past several decades, exploring the pathogenesis of MI is crucial. The apoptosis of cardiomyocytes resulting from MI has been identified as an essential process in the progression to heart failure [7]. Thus, to
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