microRNA-107 inhibits gastric cancer cell proliferation and metastasis by targeting PI3K/AKT pathway

• Published in: Microbial pathogenesis 2018-08, Vol.121, p.110-114
• Main Authors: Cheng, Feng, Yang, Zhijun, Huang, Fei, Yin, Liangqiong, Yan, Guosheng, Gong, Guofu
• Format: Article
• Language: English
• Subjects: Animals; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation; Gene Targeting; Humans; Luciferase activity; Male; Metastasis; Mice; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Transfection; Transwell invasion; Wound-healing; Xenograft Model Antitumor Assays
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2018.04.060

The present study was aimed to investigate the effect of miR-107 transfection on gastric cancer cell growth. Results from qRT-PCR revealed that level of miR-107 in SGC-7901 and MKN1 cell lines was down-regulated in comparison to the normal cells, GES-1. CCK-8 assay revealed a significant reduction in the proliferation of SGC-7901 cells on transfection with miR-107. The tumor growth was very slow in the mice implanted with SGC-7901/miR-107 compared to those bearing SGC-7901/miR-NC. In SGC-7901 cells metastasis potential after miR-107 transfection was examined using wound-healing and Transwell invasion assays. The migration as well as invasion potential of SGC-7901 cells was significantly lower on transfection with miR-107. The activity of luciferase was reduced markedly in SGC-7901 cells co-transfected with miR-107 mimic compared to miR-NC. However, miR-107 mimic co-transfection did not affect the luciferase activity in SGC-7901 cells bearing mutant-type BDNF 3′UTR. Western blot assay showed that miR-107 overexpression causes inhibition of BDNF mRNA and protein expression in SGC-7901 cells. The CCK8 assay showed that pBDNF transfection prevented miR-107 mediated inhibition of SGC-7901 cell proliferation. miR-107 mimic transfection inhibited expression of BDNF and activation of PI3K (p-PI3K) and AKT (p-AKT) in SGC-7901 cells. In order to confirm whether activation of PI3K and AKT by miR-107 mimic involves inhibition of BDNF, the cells were co-transfected with si-BDNF. The results revealed that si-BDNF transfection led to inhibition of BDNF expression and PI3K and AKT activation in SGC-7901 cells. In summary, the present study demonstrates that miR-107 expression inhibits proliferation and metastasis in gastric cancer cells. Therefore, miR-107 acts as tumor inhibitor for gastric cancer through targeting BDNF expression. Thus miR-107 can be used for treatment of gastric cancer. •miR-107 transfection reduces gastric cancer cell proliferation.•It suppresses tumor growth in mice implanted with SGC-7901.•Cancer cell metastasis is also inhibited by miR-107 transfection.•miR-107 inhibits BDNF mRNA and protein expression in SGC-7901 cells.•The activation of PI3K and AKT in SGC-7901 cells also inhibited.