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

作者:Xiao Lin, Junkun Zhan, Jia‐Yu Zhong, Yanjiao Wang, Yi Wang, Shuang Li, Jieyu He, Pan Tan, Yiyin Chen, Xuebin Liu, Xing‐Jun Cui, You‐Shuo Liu · 发表于:Aging · 年份:2019 · DOI:10.18632/aging.101758 · 被引用次数:71 · 研究领域:Cancer-related molecular mechanisms research、MicroRNA in disease regulation、Circular RNAs in diseases

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.