lncRNA-ES3/miR-34c-5p/BMF axis is involved in regulating high-glucose-induced calcification/senescence of VSMCs

Aging (Albany NY). 2019 Jan 17;11(2):523-535. doi: 10.18632/aging.101758.

Abstract

Vascular calcification/aging is common in diabetes and is associated with increased morbidity and mortality of patients. MiR-34c-5p, not miR-34c-3p, was suppressed significantly in calcification/senescence of human aorta vascular smooth muscle cells (HA-VSMCs) induced by high glucose, which was proven by the formation of mineralized nodules and staining of senescence associated-β-galactosidase staining (SA β-gal) positive cells. Overexpression of miR-34c-5p alleviated calcification/senescence of HA-VSMCs, whereas inhibition of miR-34c-5p received the opposite results. Bcl-2 modifying factor (BMF) was a functional target of miR-34c-5p and it was involved in the process of calcification/senescence of HA-VSMCs. Besides, lncRNA-ES3 acted as a competing endogenous RNAs (ceRNA) of miR-34c-5p to enhance BMF expression. Further, lncRNA-ES3 inhibited miR-34c-5p expression by direct interaction and its knockdown suppressed the calcification/senescence of HA-VSMCs. Our results showed for the first time that the calcification/senescence of VSMCs was regulated by lncRNA-ES3 /miR-34c-5p/BMF axis.

Keywords: BMF; VSMCs calcification/senescence; diabetes; lncRNA-ES3; miR-34c-5p; vascular aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Calcinosis / chemically induced
  • Cellular Senescence / drug effects*
  • Gene Expression Regulation / drug effects
  • Glucose / toxicity*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • RNA, Long Noncoding / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • BMF protein, human
  • MIRN34 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Glucose