CircRNA LRP6 Promotes High-glucose Induced Proliferation and Migration of Vascular Smooth Muscle Cells Through Regulating MiR-545-3p/HMGA1 Signaling Axis

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2021 Sep 20

PMID 34540004

Citations 5

Authors

Yuanyuan Bai

Feng Liu

Zili Yang

Affiliations

Soon will be listed here.

Abstract

Objective: The dysfunction of vascular smooth muscle cells (VSMCs) has been revealed to be closely linked with the pathogenesis of cardiovascular diseases in diabetes. Recently, circular RNAs (circRNAs) were found to regulate the behaviors of VSMCs. Here, we attempted to study the role of circLRP6 in VSMCs under diabetes condition.

Methods: Human VSMCs were cultured under the condition of normal glucose (NG) or high glucose (HG). VSMC viability and proliferation were estimated by CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. VSMC migration and invasion were assessed via wound-healing and transwell experiments. Protein expression of HMGA1 was measured in VSMCs using western blot and immunofluorescence analysis. Relative expressions of circLRP6, miR-545-3p, and HMGA1 mRNA were estimated in VSMCs using qRT-PCR. The co-localization of circLRP6 and miR-545-3p was verified by fluorescence in situ hybridization (FISH) analysis. Binding sequence of miR-545-3p in circLRP6 or HMGA1 was predicted using StarBase tool, and verified by RNA immunoprecipitation and dual-luciferase reporter experiments.

Results: HG exposure promoted VSMC proliferation, migration and invasion, upregulated the circLRP6 expression, and downregulated HMGA1 expression. Knockdown of circLRP6 or overexpression of miR-545-3p abrogated the HG-caused VSMC proliferation, migration and invasion. CircLRP6 severed as a miR-545-3p sponge, and HMGA1 was targeted by miR-545-3p. MiR-545-3p inhibitor blocked the suppressive effects of si-circLRP6 on VSMC in the presence of HG.

Conclusion: These findings suggest that circRNA LRP6 promotes HG-induced VSMC proliferation and migration through regulating miR-545-3p/HMGA1 signaling axis.

Citing Articles

Circular RNAs in human diseases.

Wang Y, Zhang J, Yang Y, Liu Z, Sun S, Li R MedComm (2020). 2024; 5(9):e699.

PMID: 39239069 PMC: 11374765. DOI: 10.1002/mco2.699.

[Research advances on the mechanism of circular RNA in diabetic wound healing].

Nong Y, Lyu X Zhonghua Shao Shang Yu Chuang Mian Xiu Fu Za Zhi. 2023; 39(5):487-490.

PMID: 37805760 PMC: 11630309. DOI: 10.3760/cma.j.cn501225-20220727-00317.

Circular RNA as Therapeutic Targets in Atherosclerosis: Are We Running in Circles?.

Triska J, Mathew C, Zhao Y, Chen Y, Birnbaum Y J Clin Med. 2023; 12(13).

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The progress and challenges of circRNA for diabetic foot ulcers: A mini-review.

Li D, Guo J, Ni X, Sun G, Bao H Front Endocrinol (Lausanne). 2022; 13:1019935.

PMID: 36531481 PMC: 9747764. DOI: 10.3389/fendo.2022.1019935.

Circular RNAs in diabetes and its complications: Current knowledge and future prospects.

Yin W, Zhang Z, Xiao Z, Li X, Luo S, Zhou Z Front Genet. 2022; 13:1006307.

PMID: 36386812 PMC: 9643748. DOI: 10.3389/fgene.2022.1006307.

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