Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1: Epigenetic Regulation of PTEN in Mediating Vascular Smooth Muscle Cell Proliferation and Apoptosis

IF 0.9 4区 材料科学 Science of Advanced Materials Pub Date : 2023-05-01 DOI:10.1166/sam.2023.4485
Anas O. K. Abu Bokha, Mingyang Song, Chen-He Li, Ahmad M. Zalloom, Rui Li
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Abstract

This study investigated the regulatory role of long non-coding RNA (lncRNA) MALAT1 in HA-VSMCs proliferation and apoptosis through mediating PTEN level. HA-VSMCs were induced with different doses of ox-LDL for various time points, and the relative level of MALAT1 was determined. MALAT1 was upregulated in a time- and dose-dependent manner. Overexpression of MALAT1 increased viability and proliferative rate, and decreased apoptotic rate of HA-VSMCs induced with 100 mg/L ox-LDL for 24 h, which was reversed by si-MALAT1 transfection. PTEN protein level was downregulated by ox-LDL induction and upregulated by si-MALAT1. MALAT1 was mainly distributed in the nucleus, and it interacted with EZH2. Silencing of MALAT1 attenuated EZH2 binding on PTEN promoter region. Knockdown of PTEN reversed the decreased proliferative ability and increased apoptotic rate in ox-LDL-induced HA-VSMCs transfected with si-MALAT1. These results indicate that MALAT1 accelerates HA-VSMCs proliferation by recruiting EZH2 to mediate PTEN level. Overall, MALAT1 may play a crucial role in the progression of atherosclerosis and may be a potential therapeutic target.
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长链非编码RNA转移相关肺腺癌转录物1:PTEN介导血管平滑肌细胞增殖和凋亡的表观遗传调控
本研究探讨了长非编码RNA(lncRNA)MALAT1通过介导PTEN水平对HA VSMCs增殖和凋亡的调节作用。用不同剂量的ox-LDL在不同时间点诱导HA VSMCs,并测定MALAT1的相对水平。MALAT1以时间和剂量依赖的方式上调。MALAT1的过表达增加了用100mg/L ox-LDL诱导24小时的HA VSMCs的生存能力和增殖率,并降低了其凋亡率,这通过si-MALAT1转染而逆转。ox-LDL诱导PTEN蛋白水平下调,si-MALAT1上调。MALAT1主要分布于细胞核内,与EZH2相互作用。MALAT1的沉默减弱了EZH2与PTEN启动子区的结合。PTEN的敲除逆转了用si-MALAT1转染的ox-LDL诱导的HA VSMCs中增殖能力的降低和凋亡率的增加。这些结果表明,MALAT1通过募集EZH2介导PTEN水平来加速HA VSMCs的增殖。总体而言,MALAT1可能在动脉粥样硬化的进展中发挥关键作用,并可能成为潜在的治疗靶点。
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来源期刊
Science of Advanced Materials
Science of Advanced Materials NANOSCIENCE & NANOTECHNOLOGY-MATERIALS SCIENCE, MULTIDISCIPLINARY
自引率
11.10%
发文量
98
审稿时长
4.4 months
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