LncRNA HOTAIR regulates the proliferation and apoptosis of vascular smooth muscle cells through targeting miRNA-130b-3p/PPARα axis

H. Xue, B. Wang, Y.-S. Xue

Department of Human Anatomy and Histology and Embryology, School of Basic Medicine, Air Force Medical College, Xi’an, China. xys978088@163.com

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• Cardiology

OBJECTIVE: To investigate the role of long non-coding RNA (lncRNA) HOTAIR in influencing the proliferative and apoptotic abilities of vascular smooth muscle cells (VSMCs) by regulating microRNA-130b-3p (miRNA-130b-3p)/peroxisome proliferator-activated receptor alpha (PPARα) axis.

MATERIALS AND METHODS: The expression levels of HOTAIR, miRNA-130b-3p, and PPARα in VSMCs treated with different doses of ox-LDL for different time points were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The subcellular distribution of HOTAIR in VSMCs was examined. The regulatory effects of HOTAIR, miRNA-130b-3p, and PPARα on the viability and apoptosis of ox-LDL-treated with VSMCs were assessed. The interaction among HOTAIR, miRNA-130b-3p, and PPARα was evaluated through Dual-luciferase reporter gene assay and Western blot.

RESULTS: After treatment of different doses of ox-LDL in VSMCs, the levels of HOTAIR and PPARα were gradually downregulated, whereas miRNA-130b-3p was upregulated. The overexpression of HOTAIR reversed the enhanced viability and suppressed apoptosis in ox-LDL-treated VSMCs. HOTAIR was mainly distributed in nucleus of VSMCs. MiRNA-130b-3p was the direct target of HOTAIR and its level was negatively regulated by HOTAIR. Moreover, miRNA-130b-3p could bind to PPARα and could negatively regulate its level. The knockdown of HOTAIR could reverse the regulatory effect of PPARα on the proliferative and apoptotic abilities of VSMCs

CONCLUSIONS: HOTAIR reduces the proliferative ability and stimulates the apoptosis in ox-LDL-treated VSMCs by targeting miRNA-130b-3p/PPARα axis.

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