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CircHIPK3 Alleviates High Glucose Toxicity to Human Renal Tubular Epithelial HK-2 Cells Through Regulation of miR-326/miR-487a-3p/SIRT1

Authors Zhuang L, Wang Z, Hu X, Yang Q, Pei X, Jin G

Received 30 October 2020

Accepted for publication 7 January 2021

Published 17 February 2021 Volume 2021:14 Pages 729—740

DOI https://doi.org/10.2147/DMSO.S289624

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Ming-Hui Zou


Langen Zhuang, Ziwei Wang, Xiaolei Hu, Qingqing Yang, Xiaoyan Pei, Guoxi Jin

Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004 Anhui, People’s Republic of China

Correspondence: Guoxi Jin
Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China
Tel +86-18096530238
Email guoxijinnfm@163.com

Background: The intervention of circular RNA HIPK3 (circHIPK3) in diabetes has drawn increasing attention in recent years. However, the underlying mechanism of circHIPK3 in diabetic nephropathy (DN) has not been fully elucidated. Thus, the current study aims to investigate the role of circHIPK3 in high glucose (HG)-induced toxicity to human renal tubular epithelial HK-2 cells.
Methods: The expression of circHIPK3 in HK-2 cells induced by HG was determined by qRT-PCR and Western blot. The regulatory effects of circHIPK3 and miR-326/miR-487a-3p on cells proliferative and apoptosis were evaluated by CCK-8 and flow cytometry. Dual-luciferase reporter assay was applied to predict the target genes of miR-326 or miR-487a-3p.
Results: Expression level of circHIPK3 in HK-2 cells was remarkably decreased after the treatment of HG. The overexpression of circHIPK3 effectively reversed the HG-induced HK-2 cell proliferation inhibition and apoptosis. Furthermore, SIRT1 was confirmed to be the target gene of miR-326 and miR-487a-3p, which were showed to be the downstream genes of circHIPK3. The silencing of miR-326 or miR-487a-3p was also proved to induce proliferation and reduce apoptosis in HG-induced HK-2 cells.
Conclusion: Our data suggest that overexpression of circHIPK3 can attenuate the proliferation inhibition of HK-2 induced by HG and inhibit apoptosis through sponging miR-326 or miR-487a-3p to regulate SIRT1.

Keywords: diabetic nephropathy, high glucose, circHIPK3, miR-326, miR-487a-3p, SIRT1

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