Inhibiting lncRNA ROR suppresses growth, migration and angiogenesis in microvascular endothelial cells by up-regulating miR-26

Eur Rev Med Pharmacol Sci. 2018 Nov;22(22):7985-7993. doi: 10.26355/eurrev_201811_16427.

Abstract

Objective: Lower extremity arteriosclerosis is one of leading causes of death worldwide. Arteriosclerosis is closely related to microvascular endothelial cells. This study was aimed to explore the role of long non-coding RNA ROR in regulations of growth, migration, and angiogenesis of microvascular endothelial cells.

Materials and methods: Angiogenesis was determined by the number of tube-like cells on a matrigel extracellular matrix. Cell viability, apoptosis, and migration were determined by CCK-8 assay, PI/FITC-Annexin V staining method, and transwell assay, respectively. Relative RNA expression of ROR, miR-26, and angiogenesis-associated genes were analyzed by qRT-PCR. The protein expression of apoptosis- and angiogenesis-associated genes, as well as main factors in NF-κB and JAK1/STAT3 pathways, were analyzed by Western blot.

Results: LncRNA ROR silence inhibited viability, migration, and angiogenesis of HMEC-1 cells but promoted apoptosis of them. miR-26 expression was promoted after knocking down ROR expression. miR-26 overexpression enhanced the inhibitory effects of ROR silence on growth, migration, and angiogenesis in HMEC-1 cells, whereas, miR-26 silence impaired the effects of ROR silence. Finally, we found that NF-κB and JAK1/STAT3 signaling pathways were inhibited by ROR down-regulation. Similarly, miR-26 overexpression enhanced the inhibitory effect of ROR down-regulation on the pathways and miR-26 inhibition abrogated it.

Conclusions: Down-regulating lncRNA ROR inhibited growth, migration and angiogenesis of microvascular endothelial cells possibly through up-regulation of miR-26. During this process, the activations of NF-κB and JAK1/STAT3 pathways were inhibited after interaction of ROR and miR-26.

MeSH terms

  • Apoptosis / physiology
  • Cell Line
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Cell Survival / physiology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism*
  • Humans
  • MicroRNAs / biosynthesis*
  • Microvessels / metabolism*
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation / physiology

Substances

  • Linc-RNA-RoR, human
  • MIRN26A microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding