title: Long noncoding RNA H19-derived miR-675 aggravates restenosis by targeting PTEN.
abstract: Restenosis is mainly attributed to excessive proliferation of vascular smooth muscle cells (VSMCs). Noncoding RNAs have been identified as key regulators of diverse pathological processes. We reported that the long noncoding RNA H19 (LncRNA H19) and LncRNA H19-derived microRNA (miR-675) are overexpressed in neointima of balloon-injured artery. Thus, the present study aims to evaluate the role of LncRNA H19 on VSMCs proliferation. To determine the changes of LncRNA H19 and miR-675 expression in the injured arterial wall, the standard rat carotid artery balloon injury model was used. In vivo studies demonstrated that both LncRNA H19 and miR-675 were upregulated after vascular injury. Correlation analysis revealed a positive relationship between LncRNA H19/miR-675 and the ratio of intima to media. Gain-of-function studies showed that the overexpression of LncRNA H19 accelerated T/G HA-VSMC proliferation in vitro. We further validated that PTEN is the target gene of miR-675 as demonstrated by luciferase assay. Finally, the results of the rescue experiment indicated that LncRNA H19 promoted the proliferation of T/G HA-VSMC in a miR-675-dependent manner. This finding not only reveal a novel function of LncRNA H19, but also has important diagnostic and therapeutic implications in the setting of restenosis and perhaps other vascular proliferative disorders as well.
authors.affiliation: Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Junyuan
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, 110122, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Ruoran
authors.initials: R
authors.lastname: Lin
authors.affiliation: Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Lun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, School of Pharmacy, Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, 110122, China.
authors.forename: Huize
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, 110001, China. Electronic address: sjxin@cmu.edu.cn.
authors.forename: Shijie
authors.initials: S
authors.lastname: Xin
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries; D049109:Cell Proliferation; D006083:Graft Occlusion, Vascular / Q000139:chemically induced / Q000473:pathology*; D035683:MicroRNAs / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors*; D062085:RNA, Long Noncoding / Q000235:genetics*; D051381:Rats
chemical_list: C094335:H19 long non-coding RNA; C000626775:MIRN675 microRNA, rat; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat
keywords: H19; Noncoding RNAs; Restenosis; Vascular smooth muscle cells; miR-675