LncRNA APOA1-AS facilitates proliferation and migration and represses apoptosis of VSMCs through TAF15-mediated SMAD3 mRNA stabilization
LncRNA APOA1-AS facilitates proliferation and migration and represses apoptosis of VSMCs through TAF15-mediated SMAD3 mRNA stabilization
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DOI：
10.1080/15384101.2021.1951940
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发表时间：
2021-08-12
期刊：
影响因子：
4.3
通讯作者：
Zheng, Junyi
中科院分区：
文献类型：
--
作者：
Wang, Jixiang;Cai, Ying;Zheng, Junyi
冠状动脉粥样硬化（CAS）是心血管疾病的主要原因。长链非编码RNA（lncRNA）已被认为是冠状动脉疾病（CAD）的新生物标志物。载脂蛋白A1反义RNA（APOA 1-AS）在动脉粥样硬化形成过程中呈高表达，但其在动脉粥样硬化形成中的作用机制尚未见报道。因此，本文旨在探讨APOA 1-AS在CAS中的作用。用氧化低密度脂蛋白（ox-LDL）处理血管平滑肌细胞（VSMCs）以模拟动脉粥样硬化样损伤。实时定量PCR（RT-qPCR）和蛋白质印迹分析分析基因表达。采用CCK-8试剂盒、创伤愈合实验和流式细胞术检测APOA 1-AS对VSMCs病理表型的调节作用。结果表明，ox-LDL处理的VSMCs（ox-LDL-VSMCs）中APOA 1-AS表达显著上调。载脂蛋白A1-AS的缺乏可抑制ox-LDL-VSMCs的增殖和迁移，并促进其凋亡。在机制上，APOA 1-AS募集TATA盒结合蛋白相关因子15（TAF 15）蛋白以稳定SMAD家族成员3（SMAD 3）mRNA并激活TGF-β/SMAD 3信号通路。总之，APOA 1-AS通过TAF 15介导的SMAD 3 mRNA稳定作用促进VSMCs增殖、迁移和抑制凋亡，提示APOA 1-AS可能是CAS的一个靶点。
Coronary atherosclerosis (CAS) is a major cause of cardiovascular disease. Long non-coding RNAs (lncRNAs) have been implicated as novel biomarkers in coronary artery disease (CAD). APOA1 antisense RNA (APOA1-AS) was proven to show high expression during atherosclerotic development, but no report has uncovered the detailed mechanism of APOA1-AS in CAS. Thus, this paper aims to explore the role of APOA1-AS in CAS. Vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL) to mimic atherosclerosis-like injury. Quantitative real-time PCR (RT-qPCR) and western blot analysis analyzed gene expression. Cell counting kit-8 (CCK-8), wound healing assay, and flow cytometry were implemented to assess the function of APOA1-AS in modulating pathological phenotype of VSMCs. Results demonstrated that APOA1-AS was notably up-regulated in ox-LDL treated VSMCs (ox-LDL-VSMCs). The deficiency of APOA1-AS hindered proliferation and migration and stimulated apoptosis in ox-LDL-VSMCs. Mechanistically, APOA1-AS recruited TATA-box binding protein associated factor 15 (TAF15) protein to stabilized SMAD family member 3 (SMAD3) mRNA and activate the TGF-beta/SMAD3 signaling pathway. In conclusion, APOA1-AS contributed to proliferation and migration and repressed apoptosis of VSMCs through TAF15-mediated SMAD3 mRNA stabilization, indicating that APOA1-AS could be a promising target for CAS.