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Circ_0068655 Promotes Cardiomyocyte Apoptosis via miR-498/PAWR Axis

Tissue Engineering and Regenerative Medicine 2020년 17권 5호 p.659 ~ 670
Chai Qiaoying, Zheng Mingqi, Wang Le, Wei Mei, Yin Yajuan, Ma Fangfang, Li Xinping, Zhang Haijun, Liu Gang,
소속 상세정보
 ( Chai Qiaoying ) - Hebei Medical University First Hospital Department of Cardiovasology
 ( Zheng Mingqi ) - Hebei Medical University First Hospital Department of Cardiovasology
 ( Wang Le ) - Hebei Medical University First Hospital Department of Cardiovasology
 ( Wei Mei ) - Hebei Medical University First Hospital Department of Cardiovasology
 ( Yin Yajuan ) - Hebei Medical University First Hospital Department of Cardiovasology
 ( Ma Fangfang ) - Hebei Medical University First Hospital Department of Cardiovasology
 ( Li Xinping ) - Han Dan First Hospital Department of Cardiovasology
 ( Zhang Haijun ) - Han Dan First Hospital Department of Cardiovasology
 ( Liu Gang ) - Hebei Medical University First Hospital Department of Cardiovasology

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.

키워드

Circular RNA; Myocardial infarction; MiR-498; PAWR; Cardiomyocyte apoptosis

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