Long non‐coding RNA XIST expedites lung adenocarcinoma progression through upregulating MDM2 expression via binding to miR‐363‐3p

作者：Hao Rong, Bing Chen, Xing Wei, Jun Peng, Ke Ma, Song Duan, Jintao He · 发表于：Thoracic Cancer · 年份：2020 · DOI：10.1111/1759-7714.13310 · 被引用次数：26 · 研究领域：Cancer-related molecular mechanisms research、Circular RNAs in diseases、Kruppel-like factors research

BACKGROUND: Lung adenocarcinoma (LAD) is a highly aggressive malignant tumor which threatens the health and life of the population. Long non-coding RNA X-inactive specific transcript (XIST) and mouse double minute clone 2 (MDM2) are connected with the tumorigenesis of LAD. Nevertheless, whether MDM2 is regulated by XIST has not previously been reported in LAD. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of XIST, microRNA-363-3p (miR-363-3p) and MDM2 in LAD tissues and cells. The proliferation, migration, invasion and apoptosis of LAD cells were determined by 3-(4, 5-dimethylthiazol-2-YI)-2, 5-diphenyltetrazolium bromide (MTT), transwell or flow cytometry assay, respectively. MDM2 protein level was detected using western blot analysis. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pulldown assay were performed to determine the interaction among XIST, miR-363-3p and MDM2. A xenograft tumor model was constructed to validate the effect of XIST on LAD cells in vivo. RESULTS: We found that XIST and MDM2 were remarkably elevated while miR-363-3p was reduced in LAD tissues and cells. Both XIST and MDM2 downregulation restrained proliferation, migration and invasion, and facilitated apoptosis of LAD cells in vitro. Importantly, XIST bound to miR-363-3p to modulate MDM2 expression in LAD cells. Moreover, miR-363-3p knockdown or MDM2 elevation reversed the effects of XIST downregulation on the pr...