Circular RNA CircGlis3 Protects Against Islet β-cell Dysfunction and Apoptosis in Obesity

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Jan 21

PMID 36681689

Authors

Yue Liu

Yue Yang

Chenying Xu

Jianxing Liu

Jiale Chen

Guoqing Li

Bin Huang

Yi Pan

Yanfeng Zhang

Qiong Wei

Stephen J Pandol

Fangfang Zhang

Ling Li

Liang Jin

Affiliations

Soon will be listed here.

Abstract

Pancreatic β-cell compensation is a major mechanism in delaying T2DM progression. Here we report the abnormal high expression of circGlis3 in islets of male mice with obesity and serum of people with obesity. Increasing circGlis3 is regulated by Quaking (QKI)-mediated splicing circularization. circGlis3 overexpression enhances insulin secretion and inhibits obesity-induced apoptosis in vitro and in vivo. Mechanistically, circGlis3 promotes insulin secretion by up-regulating NeuroD1 and Creb1 via sponging miR-124-3p and decreases apoptosis via interacting with the pro-apoptotic factor SCOTIN. The RNA binding protein FUS recruits circGlis3 and collectively assemble abnormal stable cytoplasmic stress granules (SG) in response to cellular stress. These findings highlight a physiological role for circRNAs in β-cell compensation and indicate that modulation of circGlis3 expression may represent a potential strategy to prevent β-cell dysfunction and apoptosis after obesity.

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