Low expression of lncRNA-GAS5 is implicated in human primary varicose great saphenous veins

• Published in: PloS one Vol. 10; no. 3; p. e0120550
• Main Authors: Li, Li, Li, Xiang, The, Erlinda, Wang, Li-Jie, Yuan, Tian-You, Wang, Shi-Yi, Feng, Jing, Wang, Jing, Liu, Yuan, Wu, Ya-Han, Ma, Xiu-E, Ge, Jin, Cui, Ying-Yu, Jiang, Xiao-Yan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.03.2015; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Annexin A2 - chemistry; Annexin A2 - metabolism; Annexins; Apoptosis; Breast cancer; Calcium ions; Calcium-binding protein; Cardiac arrhythmia; Cardiology; Cell cycle; Cell growth; Cell migration; Cell Movement; Cell Proliferation; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cyclin-Dependent Kinase Inhibitor p27 - genetics; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Education; Extracellular matrix; Female; Hospitals; Humans; Kinases; Laboratories; Male; Medicine; Middle Aged; Muscles; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - metabolism; Pathogenesis; Pathology; Protein Binding; Proteins; Ribonucleic acid; RNA; RNA Interference; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Small Interfering - metabolism; RNA-binding protein; Saphenous Vein - cytology; Smooth muscle; Transcription; Ultrasonic imaging; Veins; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120550

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.