Tissue Eng Regen Med.  2020 Oct;17(5):659-670. 10.1007/s13770-020-00270-8.

Circ_0068655 Promotes Cardiomyocyte Apoptosis via miR-498/ PAWR Axis

Affiliations
  • 1Department of Cardiovasology, the First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang, Hebei 050031, China
  • 2Department of Cardiovasology, Han Dan First Hospital, No. 24, Congtai Road, Congtai District, Handan, Hebei 056001, China

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.

Keyword

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