circRNA_0084043 contributes to the progression of diabetic retinopathy via sponging miR-140-3p and inducing TGFA gene expression in retinal pigment epithelial cells.

Abstract

Diabetic retinopathy (DR) is a frequent complication of diabetes and it can lead to visual impairment and blindness. However, the mechanism of their regulation remains little known. circRNAs can function as crucial competing endogenous RNA, which can sponge corresponding miRNAs and affect mRNA expression in various diseases, including DR. In our current research, we observed that circRNA_0084043 was elevated in high glucose (HG)-incubated ARPE-19 cells. Then, we focused on whether and how circRNA_0084043 participated in retinal vascular dysfunction under conditions diabetes. Apoptosis, inflammation and oxidative stress are hallmark of DR progression. This work was aimed to investigate the signaling mechanisms of circRNA_0084043 in these pathogenesis of DR. We discovered loss of circRNA_0084043 significantly increased cell survival and repressed HG-triggered apoptosis. In addition, knockdown of circRNA_0084043 remarkably reduced oxidative stress as evidenced by the down-regulated malondialdehyde (MDA) content, enhanced activities of Super Oxide Dismutase (SOD) and Glutathione peroxidase (GSH-PX). Addition, silence of circRNA_0084043 effectively restrained HG-stimulated inflammation as proved by repressing inflammatory cytokines Tumor Necrosis Factor α (TNF-α), Interleukin 6 (IL-6) and Cox-2 in ARPE-19 cells. Subsequently, we successfully predicted that miR-140-3p was a downstream target of circRNA_0084043, which could be negatively regulated by circRNA_0084043. Mechanistically, loss of miR-140-3p abrogated the beneficial effects of circRNA_0084043 siRNA on ARPE-19 cells. Transforming Growth Factor alpha (TGFA) can exhibit a role in multiple diseases. Taken these together, these data demonstrated that loss of circRNA_0084043 depressed HG-induced damage via sponging miR-140-3p and regulating TGFA.

• Authors: Ying Li, Ting Cheng, Chengliang Wan, Yanhong Cang
• Journal: Gene (Gene) Vol. 747 Pg. 144653 (Jul 15 2020) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 32259630 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• MicroRNAs
• Mirn140 microRNA, human
• RNA, Circular
• TGFA protein, human
• Transforming Growth Factor alpha
• Glucose

Topics

• Apoptosis (drug effects)
• Base Sequence
• Cell Line
• Cell Proliferation (drug effects)
• Diabetic Retinopathy (genetics)
• Disease Progression
• Down-Regulation (drug effects, genetics)
• Epithelial Cells (drug effects, metabolism, pathology)
• Gene Expression Regulation (drug effects)
• Glucose (toxicity)
• Humans
• Inflammation (pathology)
• MicroRNAs (genetics, metabolism)
• Models, Biological
• Oxidative Stress (drug effects)
• RNA, Circular (genetics, metabolism)
• Retinal Pigment Epithelium (pathology)
• Transforming Growth Factor alpha (genetics, metabolism)
• Up-Regulation (drug effects, genetics)