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

• Chai Q
• Zheng M
• Wang Z
• We M
• Yin Y
• Ma F
• Li X
• Zhang H
• Liu G

• KMID: 2507318
• DOI: http://doi.org/10.1007/s13770-020-00270-8

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