Circular RNA circ_0029589 regulates proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs by regulating miR-424-5p/IGF2 axis.

Abstract

BACKGROUND:

Circular RNAs (circRNAs) have been identified to be critical mediators in the progression of atherosclerosis (AS). However, the exact roles and molecular mechanism of circ_0029589 in AS are far from understood.

METHODS:

Vascular smooth muscle cells (VSMCs) stimulated by oxidized low-density lipoprotein (ox-LDL) were served as a cellular model of AS. The expression levels of circ_0029589, microRNA (miR)-424-5p, and insulin-like growth factor 2 (IGF2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot analysis. Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell apoptosis, migration and invasion were examined by flow cytometry and transwell assay. The relationship between miR-424-5p and circ_0029589 or IGF2 was predicted by starbase and verified by dual-luciferase reporter assay.

RESULTS:

Circ_0029589 and IGF2 were upregulated and miR-424-5p was downregulated in VSMCs treated with ox-LDL. Silence of circ_0029589 inhibited proliferation, migration and invasion but induced apoptosis in ox-LDL-treated VSMCs. MiR-424-5p was a target of circ_0029589 and its knockdown reversed the effects of circ_0029589 interference on proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs. IGF2 was a target of miR-424-5p and miR-424-5p overexpression suppressed proliferation, migration and invasion while promoted apoptosis in ox-LDL-treated VSMCs by downregulating IGF2. Circ_0029589 positively modulated IGF2 expression by sponging miR-424-5p.

CONCLUSION:

Circ_0029589 silence might inhibit the progression of AS by regulating miR-424-5p/IGF2 axis, providing a novel mechanism for pathogenesis of AS.

• Authors: Hui Yu, Luosha Zhao, Yang Zhao, Jiayue Fei, Wenli Zhang
• Journal: Vascular pharmacology (Vascul Pharmacol) Vol. 135 Pg. 106782 (12 2020) ISSN: 1879-3649 [Electronic] United States
• PMID: 32860985 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• IGF2 protein, human
• Lipoproteins, LDL
• MIRN424 microrna, human
• MicroRNAs
• RNA, Circular
• oxidized low density lipoprotein
• Insulin-Like Growth Factor II

Topics

• Apoptosis (drug effects)
• Atherosclerosis (genetics, metabolism, pathology)
• Case-Control Studies
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Gene Expression Regulation
• Humans
• Insulin-Like Growth Factor II (genetics, metabolism)
• Lipoproteins, LDL (pharmacology)
• MicroRNAs (genetics, metabolism)
• Muscle, Smooth, Vascular (drug effects, metabolism, pathology)
• Myocytes, Smooth Muscle (drug effects, metabolism, pathology)
• RNA, Circular (genetics, metabolism)
• Signal Transduction