title: MicroRNA-365 inhibits the proliferation of vascular smooth muscle cells by targeting cyclin D1.
abstract: Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of disease progression in atherosclerosis. Cell proliferation is regulated by cell cycle regulatory proteins. MicroRNAs (miR) have been reported to act as important gene regulators and play essential roles in the proliferation and migration of VSMCs in a cardiovascular disease. However, the roles and mechanisms of miRs in VSMCs and neointimal formation are far from being fully understood. In this study, cell cycle-specific cyclin D1 was found to be a potential target of miR-365 by direct binding. Through an in vitro experiment, we showed that exogenous miR-365 overexpression reduced VSMC proliferation and proliferating cell nuclear antigen (PCNA) expression, while miR-365 was observed to block G1/S transition in platelet-derived growth factor-bb (PDGF-bb)-induced VSMCs. In addition, the proliferation of VSMCs by various stimuli, including PDGF-bb, angiotensin II (Ang II), and serum, led to the downregulation of miR-365 expression levels. The expression of miR-365 was confirmed in balloon-injured carotid arteries. Taken together, our results suggest an anti-proliferative role for miR-365 in VSMC proliferation, at least partly via modulating the expression of cyclin D1. Therefore, miR-365 may influence neointimal formation in atherosclerosis patients.
authors.affiliation: Cardiology Division, Heart Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Republic of Korea.
authors.forename: Myung-Hyun
authors.initials: MH
authors.lastname: Kim
authors.forename: Onju
authors.initials: O
authors.lastname: Ham
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Eunmi
authors.initials: E
authors.lastname: Choi
authors.forename: Chang Youn
authors.initials: CY
authors.lastname: Lee
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Jiyun
authors.initials: J
authors.lastname: Lee
authors.forename: Hyang-Hee
authors.initials: HH
authors.lastname: Seo
authors.forename: Minji
authors.initials: M
authors.lastname: Seung
authors.forename: Eunhyun
authors.initials: E
authors.lastname: Choi
authors.forename: Pil-Ki
authors.initials: PK
authors.lastname: Min
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D000077214:Becaplermin; D002339:Carotid Arteries / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000096:biosynthesis*; D015536:Down-Regulation; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000254:growth & development*; D058426:Neointima / Q000235:genetics*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011485:Protein Binding; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D016601:RNA-Binding Proteins; D051381:Rats; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics
chemical_list: C000597594:MIRN365 microRNA, rat; D035683:MicroRNAs; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D016601:RNA-Binding Proteins; D000804:Angiotensin II; D019938:Cyclin D1; D000077214:Becaplermin
keywords: CELL CYCLE; CYCLIN D1; MIR-365; PROLIFERATION; VASCULAR SMOOTH MUSCLE CELLS