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

PLoS One. 2015 Mar 25;10(3):e0120550. doi: 10.1371/journal.pone.0120550. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Annexin A2 / chemistry
  • Annexin A2 / metabolism
  • Apoptosis
  • 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
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Protein Binding
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Saphenous Vein / cytology*

Substances

  • Annexin A2
  • Cyclin-Dependent Kinase Inhibitor p21
  • GAS5 long non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Cyclin-Dependent Kinase Inhibitor p27

Grants and funding

This work was supported by the General Program of National Natural Science Foundation of China (81100551, to Xiao-Yan Jiang; 81270231, to Li Li), and the Fundamental Research Funds for the Central Universities (1500219042, to Xiao-Yan Jiang). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.