The suppression of ox-LDL-induced inflammatory response and apoptosis of HUVEC by lncRNA XIAT knockdown via regulating miR-30c-5p/PTEN axis
The suppression of ox-LDL-induced inflammatory response and apoptosis of HUVEC by lncRNA XIAT knockdown via regulating miR-30c-5p/PTEN axis
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DOI：
10.26355/eurrev_201909_18886
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Zhou, D-H
中科院分区：
文献类型：
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作者：
Hu, W-N;Duan, Z-Y;Zhou, D-H
目的：氧化型低密度脂蛋白（ox-LDL）的暴露可导致HUVEC功能障碍，从而导致动脉粥样硬化的发展，这是一种常见的炎症性血管疾病。长链非编码RNA X失活特异性转录本（XIST）已被报道与动脉粥样硬化有关。然而，这种lncRNA参与动脉粥样硬化的进展的机制是不明确的defined.MATERIALS和METHODS：HUVEC挑战ox-LDL被用作动脉粥样硬化的细胞模型。MTT法、流式细胞术和ELISA法检测细胞活力、凋亡、LDH释放和炎性细胞因子分泌。通过定量真实的时间-聚合酶链反应和蛋白质印迹法测定XIST、microRNA（miR）-30 c-5 p和10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）的表达水平。结果：ox-LDL诱导HUVEC细胞凋亡和炎症因子的释放。ox-LDL处理的HUVEC中XIST表达增强，其敲低可降低ox-LDL处理的细胞凋亡和炎症反应。MiR-30 c-5 p是XIST的靶点，其过表达抑制ox-LDL诱导的细胞凋亡和炎症反应，XIST的引入减弱了这种抑制作用。miR-30 c-5 p的作用靶点是PTEN，其干扰可显著抑制ox-LDL诱导的HUVEC细胞凋亡和炎症反应，而miR-30 c-5 p缺陷或XIST过表达可减弱这种抑制作用。
OBJECTIVE: Exposure of oxidized low-density lipoprotein (ox-LDL) could cause dysfunction of HUVEC, thus leading to atherosclerosis development, which is a common inflammatory vascular disease. Long noncoding RNA X-inactive specific transcript (XIST) has been reported to be implicated in atherosclerosis. However, the mechanism by which this lncRNA participates in the progression of atherosclerosis is poorly defined.MATERIALS AND METHODS: HUVEC challenged by ox-LDL were used as a cellular model of atherosclerosis. Cell viability, apoptosis, LDH release, and inflammatory cytokines secretion were detected by MTT, flow cytometry, and ELISA assays. The expression levels of XIST, microRNA (miR)-30c-5p, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) were measured by quantitative Real Time-Polymerase Chain Reaction and Western blot. The target interaction between XIST and miR-30c-5p or miR30c-5p and PTEN was validated by the Luciferase reporter assay and RNA immunoprecipitation.RESULTS: Treatment of ox-LDL induced cell apoptosis and inflammatory cytokines release in HUVEC. XIST expression was enhanced in HUVEC treated by ox-LDL, and its knockdown decreased cell apoptosis and inflammatory response in ox-LDL-treated cells. MiR-30c-5p was a target of XIST and its overexpression suppressed cell apoptosis and inflammatory response induced by ox-LDL, which was weakened by the introduction of XIST. PTEN was a target of miR-30c-5p, and its interference led to great inhibition of cell apoptosis and inflammatory response induced by ox-LDL in HUVEC, while this effect was attenuated by miR-30c-5p deficiency or XIST overexpression.CONCLUSIONS: XIST knockdown suppresses inflammatory response and apoptosis of HUVEC stimulated by ox-LDL by increasing miR-30c-5p and decreasing PTEN.