Department of Cardiovascular, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Eur Rev Med Pharmacol Sci. 2019 Oct;23(20):9025-9032. doi: 10.26355/eurrev_201910_19304.
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.
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.
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.
LncRNA MALAT1 mediates proliferation and apoptosis of VSMCs by sponging miRNA-124-3p to positively regulate PPARα level.
揭示长链非编码 RNA（lncRNA）MALAT1 参与血管平滑肌细胞（VSMCs）增殖和凋亡的机制。
采用实时定量聚合酶链反应（qRT-PCR）检测不同剂量氧化低密度脂蛋白（ox-LDL）作用不同时间点的 VSMCs 中 MALAT1、微小 RNA-124-3p（miRNA-124-3p）和过氧化物酶体增殖物激活受体α（PPARα）的相对水平。检测过表达 MALAT1 的 VSMCs 的增殖和凋亡变化。分析 MALAT1 的亚细胞分布。通过双荧光素酶报告基因检测确定 MALAT1、miRNA-124-3p 和 PPARα 之间的潜在结合，并确定它们的相互作用。最后，研究了 MALAT1/miRNA-124-3p/PPARα 调控环对 VSMCs 增殖和凋亡能力的影响。
ox-LDL 处理的 VSMCs 中 MALAT1 和 PPARα 呈剂量依赖性下调，而 miRNA-124-3p 逐渐上调。过表达 MALAT1 可减弱 ox-LDL 处理的 VSMCs 的活力并诱导其凋亡。此外，MALAT1 主要分布在细胞核中。双荧光素酶报告基因检测证实 MALAT1 可海绵吸附 miRNA-124-3p，且 PPARα 是 miRNA-124-3p 的直接靶标。MALAT1 负调控 miRNA-124-3p 水平，miRNA-124-3p 也负调控 PPARα 水平。最后，确定 MALAT1/miRNA-124-3p/PPARα 调控环调节 ox-LDL 处理的 VSMCs 的活力和凋亡。
lncRNA MALAT1 通过海绵吸附 miRNA-124-3p 正向调控 PPARα 水平，介导 VSMCs 的增殖和凋亡。
