PMID- 34540004 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210921 IS - 1943-8141 (Print) IS - 1943-8141 (Electronic) IS - 1943-8141 (Linking) VI - 13 IP - 8 DP - 2021 TI - CircRNA LRP6 promotes high-glucose induced proliferation and migration of vascular smooth muscle cells through regulating miR-545-3p/HMGA1 signaling axis. PG - 8909-8920 AB - 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. CI - AJTR Copyright (c) 2021. FAU - Bai, Yuanyuan AU - Bai Y AD - Department of Geriatrics, National Key Clinical Specialty, Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangzhou 510180, Guangdong, China. FAU - Liu, Feng AU - Liu F AD - Department of Geriatrics, National Key Clinical Specialty, Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangzhou 510180, Guangdong, China. FAU - Yang, Zili AU - Yang Z AD - Department of Geriatrics, National Key Clinical Specialty, Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangzhou 510180, Guangdong, China. LA - eng PT - Journal Article DEP - 20210815 PL - United States TA - Am J Transl Res JT - American journal of translational research JID - 101493030 PMC - PMC8430135 OTO - NOTNLM OT - HMGA1 OT - Vascular smooth muscle cells OT - circLRP6 OT - high glucose OT - miR-545-3p COIS- None. EDAT- 2021/09/21 06:00 MHDA- 2021/09/21 06:01 PMCR- 2021/08/15 CRDT- 2021/09/20 06:06 PHST- 2021/04/21 00:00 [received] PHST- 2021/06/11 00:00 [accepted] PHST- 2021/09/20 06:06 [entrez] PHST- 2021/09/21 06:00 [pubmed] PHST- 2021/09/21 06:01 [medline] PHST- 2021/08/15 00:00 [pmc-release] PST - epublish SO - Am J Transl Res. 2021 Aug 15;13(8):8909-8920. eCollection 2021.