LncRNA MALAT1 regulates proliferation and apoptosis of vascular smooth muscle cells by targeting miRNA-124-3p/PPARα axis

摘要

OBJECTIVE: To uncover the involvement of long non-coding RNA (lncRNA) MALAT1 in the proliferation and apoptosis of vascular smooth muscle cells (VSMCs), and the underlying mechanism. MATERIALS AND METHODS: Relative levels of MALAT1, microRNA-124-3p (miRNA-124-3p) and peroxisome proliferator-activated receptor alpha (PPARα) in VSMCs treated with different doses of oxidized low-density lipoprotein (ox-LDL) for different time points were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Proliferative and apoptotic changes of VSMCs overexpressing MALAT1 were assessed. Subcellular distribution of MALAT1 was analyzed. The potential binding among MALAT1, miRNA-124-3p and PPARα was determined by dual-luciferase reporter gene assay, and their interaction was determined as well. Finally, the influences of MALAT1/miRNA-124-3p/PPARα regulatory loop on the proliferative and apoptotic abilities of VSMCs were examined. RESULTS: MALAT1 and PPARα were dose-dependently downregulated in ox-LDL-treated VSMCs, whereas miRNA-124-3p was gradually upregulated. Overexpression of MALAT1 attenuated viability and induced apoptosis in ox-LDL-treated VSMCs. Moreover, MALAT1 was mainly distributed in the nucleus. Dual-luciferase reporter gene assay verified that MALAT1 could sponge miRNA-124-3p, and moreover, PPARα was the direct target of miRNA-124-3p. MALAT1 negatively regulated miRNA-124-3p level and miRNA-124-3p negatively regulated PPARα level as well. Finally, MALAT1/miRNA-124-3p/PPARα regulatory loop was identified to regulate the viability and apoptosis of ox-LDL-treated VSMCs. CONCLUSIONS: LncRNA MALAT1 mediates proliferation and apoptosis of VSMCs by sponging miRNA-124-3p to positively regulate PPARα level.