癌症研究
医学
小RNA
下调和上调
基因敲除
癌症
基因沉默
作者
Xin Guo,Xinxin Wang,Su-Xia Li,Yixun Lu,Tianyu Xie,Zhaoyan Qiu,Di Wu
标识
DOI:10.1093/annonc/mdz238.026
摘要
Abstract Background Chemo-resistance is one of the important causes of poor prognosis of gastric cancer patients, but the exact mechanism is still not very clear. The regulation of lncRNA and miRNA and its downstream target genes has become in focus of the field. Methods In this study, we performed lncRNA and miRNA microarray analysis of chemo-resistant cells (SGC7901/Oxaliplatin). Then, bioinformatics analysis, TaqMan real-time PCR, western blot, luciferase reporter gene assay, RNA co-immunoprecipitation, cell proliferation and apoptosis analysis were used to explicit the lncRNA-miRNA-mRNA pathway in gastric cancer chemo-resistance. Last, nude mice were used to verify the promotion of chemo-resistance in vivo. Results In this study, we identified a lncRNA-GC1, which was upregulated in chemo-resistant gastric cancer tissues and cells, and a miRNA-551b-3p, which was downregulated in chemo-resistant gastric cancer tissues and cells. Firstly, miR-551b-3p can directly bind to the non-coding region of dysbindin mRNA, thereby negatively regulating the expression of dysbindin which was involved in chemotherapy resistance in gastric cancer cells. Secondly, lncRNA-GC1 promotes chemoresistance in gastric cancer by competitively binding to miR-551b-3p to facilitate dysbindin expression in vitro and in vivo. Thirdly, the expression levels of lncRNA-GC1 were positively correlated with tumor size (P = 0.002), lymph node invasion (P = 0.001) and poor platinum response (P Conclusions LncRNA-GC1-miRNA-551b-3p-dysbindin signaling pathway may serve as a predictor for oxaliplatin response and a potential therapeutic target for gastric cancer. Legal entity responsible for the study Guo Xin. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
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