Smooth muscle enriched long non-coding RNA (SMILR) regulates cell proliferation

Margaret D. Ballantyne, Karine Pinel, Rachel Dakin, Alex T. Vesey, Louise Diver, Ruth Mackenzie, Raquel Garcia, Paul Welsh, Naveed Sattar, Graham Hamilton, Nikhil Joshi, Marc R. Dweck, Joseph M. Miano , Martin W. McBride, David E. Newby, Robert A. McDonald, Andrew H. Baker

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Phenotypic switching of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic state is implicated in diverse vascular pathologies including atherogenesis, plaque stabilisation, and neointimal hyperplasia. However, very little is known as to the role of long non coding RNA (lncRNA) during this process. Here we investigated a role for long non-coding (lnc)RNAs in VSMC biology and pathology.
METHODS AND RESULTS: Using RNA sequencing, we identified >300 lncRNAs whose expression was altered in human saphenous vein vascular smooth muscle cells following stimulation with interleukin-1α and platelet-derived growth factor. We focused on a novel lncRNA (Ensembl: RP11-94A24.1), which we termed smooth muscle–induced lncRNA enhances replication (SMILR). Following stimulation, SMILR expression was increased in both the nucleus and cytoplasm, and was detected in conditioned media. Furthermore, knockdown of SMILR markedly reduced cell proliferation. Mechanistically, we noted that expression of genes proximal to SMILR was also altered by interleukin-1α/platelet-derived growth factor treatment, and HAS2 expression was reduced by SMILR knockdown. In human samples, we observed increased expression of SMILR in unstable atherosclerotic plaques and detected increased levels in plasma from patients with high plasma C-reactive protein.
CONCLUSIONS: These results identify SMILR as a driver of vascular smooth muscle cell proliferation and suggest that modulation of SMILR may be a novel therapeutic strategy to reduce vascular pathologies.
Original languageEnglish
Pages (from-to)2050-2065
Number of pages16
JournalCirculation
Volume133
Issue number21
Early online date6 Apr 2016
DOIs
Publication statusPublished - 24 May 2016

Keywords

  • atherosclerosis
  • cell proliferation
  • microRNAs
  • RNA, untranslated
  • plasma protein, human

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