PTEN公司
张力素
生物
细胞生长
竞争性内源性RNA
细胞周期蛋白D1
分子生物学
PI3K/AKT/mTOR通路
细胞凋亡
癌症研究
免疫印迹
细胞生物学
长非编码RNA
核糖核酸
信号转导
细胞周期
基因
生物化学
作者
Yanxian Lai,Jianyong Li,Lintao Zhong,Xiang He,Xiaoyan Si,Yili Sun,Yanmei Chen,Jiayuan Zhong,Yinlan Hu,Bing Li,Wangjun Liao,Cheng Liu,Yulin Liao,Jiancheng Xiu,Jianping Bin
出处
期刊:Clinical Science
[Portland Press]
日期:2019-07-01
卷期号:133 (13): 1439-1455
被引量:24
摘要
Abstract The long non-coding RNA (lncRNA) PTENP1 is a pseudogene of phosphatase and tensin homologue deleted on chromosome ten (PTEN), has been implicated in smooth muscle cell (SMC) proliferation and apoptosis. PTENP1 is the pseudogene of PTEN. However, it is unclear whether and how PTENP1 functions in the proliferation and apoptosis of human aortic SMCs (HASMCs). Here, we hypothesised that PTENP1 inhibits HASMC proliferation and enhances apoptosis by promoting PTEN expression. PCR analysis and Western blot assays respectively showed that both PTENP1 and PTEN were up-regulated in human aortic dissection (AD) samples. PTENP1 overexpression significantly increased the protein expression of PTEN, promoted apoptosis and inhibited the proliferation of HASMCs. PTENP1 silencing exhibited the opposite effects and mitigated H2O2-induced apoptosis of HASMCs. In an angiotensin II (Ang II)-induced mouse aortic aneurysm (AA) model, PTENP1 overexpression potentiated aortic SMC apoptosis, exacerbated aneurysm formation. Mechanistically, RNA pull-down assay and a series of luciferase reporter assays using miR-21 mimics or inhibitors identified PTENP1 as a molecular sponge for miR-21 to endogenously compete for the binding between miR-21 and the PTEN transcript, releasing PTEN expression. This finding was further supported by in vitro immunofluorescent evidence showing decreased cell apoptosis upon miR-21 mimic administration under baseline PTENP1 overexpression. Ex vivo rescue of PTEN significantly mitigated the SMC apoptosis induced by PTENP1 overexpression. Finally, Western blot assays showed substantially reduced Akt phosphorylation and cyclin D1 and cyclin E levels with up-regulated PTENP1 in HASMCs. Our study identified PTENP1 as a mediator of HASMC homeostasis and suggests that PTENP1 is a potential target in AD or AA intervention.
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