Long non-coding RNA LINC00485 acts as a microRNA-195 sponge to regulate the chemotherapy sensitivity of lung adenocarcinoma cells to cisplatin by regulating CHEK1

Cancer Cell International

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[1] 0000 0004 1758 4073, grid.412604.5, Department of Respiration, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Donghu District, 330006, Nanchang, Jiangxi, People’s Republic of China;

关键词: Long intervening non-coding RNA LINC00485;    MicroRNA-195;    CHEK1;    Lung adenocarcinoma;    Competitive endogenous RNA;    Cisplatin;    Chemotherapy sensitivity;   

DOI  :  10.1186/s12935-019-0934-7

来源: publisher

【 摘 要 】

BackgroundLong non-coding RNAs (lncRNAs) are a family of non-protein-coding RNAs, which have the ability to influence the chemo-resistance of lung adenocarcinoma (LAC). In this study, we explored the mechanism by which LINC00485 competitively binds to microRNA-195 (miR-195) in the regulation of the chemotherapy sensitivity in LAC by regulating checkpoint kinase 1 (CHEK1).MethodsMicroarray analysis was used to screen out LAC related genes, and interaction between CHEK1 and miR-195, as well as that between miR-195 and LINC00485, was further confirmed by RNA-pull down and RIP. LINC00485 expression in LAC cells (A549 and H1299) was determined. The cells were then introduced with miR-195, anta-miR-195, LINC00485 or si-LINC00485 to identify the role of miR-195 and LINC00485 in LAC through evaluating the expression of CHEK1, CHEK1, Bax, Bcl-2, VEGF and HIF-1α in LAC cells by either RT-qPCR or Western blot analysis. After being treated with different concentration of cisplatin, cell proliferation, colony formation and apoptosis were assessed.ResultsLINC00485 acted as a competitive endogenous RNA against miR-195, and miR-195 directly targeted CHEK1. The expression of LINC00485 was higher in LAC cells. The down-regulation of LINC00485 or the up-regulation of miR-195 decreased the expression of CHEK1, Bcl-2, VEGF and HIF-1α, while also increasing the expression of Bax. Moreover, the over-expression of miR-195, or the silencing of LINC00485 enhanced the sensitivity of LAC cells to cisplatin, thereby promoting the apoptosis of LAC cells while suppressing the proliferation.ConclusionLINC00485 competitively binds to miR-195 to elevate CHEK1 expression in LAC cells, suggesting that LINC00485 is a novel direction for therapeutic strategies of LAC.

【 授权许可】

CC BY