The functional mechanism of miR-125b in gastric cancer and its effect on the chemosensitivity of cisplatin
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Xinyue Zhang1,*, Jie Yao2,*, Kai Guo3,*, Hu Huang4,*, Siyuan Huai1, Rui Ye1,5, Baolong Niu1, Tiannan Ji1, Weidong Han6 and Jianxiong Li7
1Department of Radiotherapy, Chinese PLA General Hospital, Beijing 100853, P.R. China
2Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R. China
3Department of Gastroenterology, The 161th Hospital of PLA, Wuhan 430010, P.R. China
4Department of Oncology, The 161th Hospital of PLA, Wuhan 430010, P.R. China
5Department of Oncology, Beidaihe Sanatorium of Beijing Military Command, Qinhuangdao 066100, P.R. China
6Department of Molecular Biology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing 100853, P.R. China
7Department of Radiotherapy, Hainan Branch of Chinese PLA General Hospital, Sanya 572000, P.R. China
*These authors have contributed equally to this work
Jianxiong Li, email: [email protected]
Weidong Han, email: [email protected]
Keywords: miR-125b; HER2; gastric cancer; cisplatin; chemosensitivity
Received: June 01, 2017 Accepted: December 05, 2017 Published: December 14, 2017
Numerous studies have shown drug resistance of gastric cancer cells could be modulated by abnormal expression of microRNAs. Cisplatin (DDP) is one of the most commonly used drugs for chemotherapy of gastric cancer. In this study, the potential function of miR-125b on DDP resistance in gastric cancer cells was investigated. Sixteen miRNAs significantly differential expressed in gastric tumor tissues and adjacent tissues were characterized and their corresponding putative target genes were also screened. MiR-125b was selected as our focus for its evident down-regulated expression among candidate genes. Real-time polymerase chain reaction assay indicated that miR-125b was significantly down-regulated in gastric cancer tissues and various cell lines. HER2 was identified as a target gene of miR-125b by dual luciferase reporter assay and Western blot. Moreover, miR-125b overexpression inhibited not only the proliferation, migration, and invasion abilities of HGC-27 and MGC-803 cells, but also in vivo tumor growth of MGC-803 cells by an intratumoral delivery approach. Notably, we observed up-regulated miR-125b contributed to the chemosensitivity of DDP in HGC-27 and MGC-803 cells at different concentrations and also possessed sensibilization for DDP at different times. MiR-125b expression was found to be related to lymph node metastasis, HER2 expression and overall survival of patients through correlation analysis. Collectively, these results indicate miR-125b may regulate DDP resistance as a promising therapeutic target for gastric cancer treatment in future.
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