title: Low expression of lncRNA-GAS5 is implicated in human primary varicose great saphenous veins.
abstract: The cellular mechanisms of primary varicose great saphenous veins (GSVs) involve inflammation, apoptosis, and proliferation of local cells and extracellular matrix degradation. Long non-coding RNAs (lncRNAs) play important roles in these cellular processes; however, which and how lncRNAs related to these mechanisms take effect on GSVs remain unclear. By screening lncRNAs that might experience changes in GSV varicosities, we selected the lower expressed lncRNA-GAS5 (growth arrest specific transcript 5) for functional assessments. Silencing of lncRNA-GAS5 promoted cell proliferation and migration, and cell cycle of the human saphenous vein smooth muscle cells (HSVSMCs), whereas overexpressing it inhibited these cellular behaviors and reduced apoptosis of HSVSMCs. RNA pull-down experiment revealed a direct bind of lncRNA-GAS5 to a Ca2+-dependent RNA-binding protein, Annexin A2. Further experiments showed that silencing of Annexin A2 reduced the HSVSMCs proliferation and vice versa. In the context of lncRNA-GAS5 knockdown, silencing of Annexin A2 reduced the proliferation of HSVSMCs while overexpression of Annexin A2 increased the proliferation. Thus, the low expression of lncRNA-GAS5 may facilitate HSVSMCs proliferation and migration through Annexin A2 and thereby the pathogenesis of GSV varicosities.
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Li
authors: L
authors: Li
authors: Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Xiang
authors: X
authors: Li
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Erlinda
authors: E
authors: The
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Li-Jie
authors: LJ
authors: Wang
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Tian-You
authors: TY
authors: Yuan
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Shi-Yi
authors: SY
authors: Wang
authors: Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Jing
authors: J
authors: Feng
authors: Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Jing
authors: J
authors: Wang
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Yuan
authors: Y
authors: Liu
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Ya-Han
authors: YH
authors: Wu
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Xiu-E
authors: XE
authors: Ma
authors: Department of Vascular Surgery, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors: Jin
authors: J
authors: Ge
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Ying-Yu
authors: YY
authors: Cui
authors: Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University School of Medicine, Shanghai 200092, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai 200092, China.
authors: Xiao-Yan
authors: XY
authors: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D017306:Annexin A2 / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012501:Saphenous Vein / Q000166:cytology*
chemical_list: D017306:Annexin A2; D050759:Cyclin-Dependent Kinase Inhibitor p21; C561567:GAS5 long non-coding RNA, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27