Up-regulated ONECUT2 and down-regulated SST promote gastric cell migration, invasion, epithelial-mesenchymal transition and tumor growth in gastric cancer

G.-H. Wang, Y.-M. Zhou, Z. Yu, J.-P. Deng, S.-F. Liu, C.-Z. Wei, Y. Feng, M. Mao, Z. Wang

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region, P.R. China. tianlei@stu.gxmu.edu.cn

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• Oncology

OBJECTIVE: Gastric cancer is a common malignancy, with high metastasis and poor prognosis. Our purpose was to explore potential molecular mechanisms of gastric cancer.

PATIENTS AND METHODS: A total of 10 pairs of gastric cancer tissues and adjacent normal gastric tissues were collected for RNA sequencing (RNA-seq), followed by differential expression analysis. Combining qRT-PCR results, two novel genes were selected for in-depth analysis, including up-regulated ONECUT and down-regulated SST. To investigate the effects of ONECUT and SST on the biological behaviors of gastric cancer cells, gastric cancer cell lines were transfected by ONECUT2 knockdown and SST overexpression. Afterwards, cell migration and invasion were examined using transwell assays, and the expressions of epithelial-mesenchymal transition (EMT)-related proteins were measured by Western blot analysis. Furthermore, cell viability was detected by CCK-8 assay. Finally, tumorigenicity in nude mice was performed.

RESULTS: Gastric cancer cell migration and invasion were inhibited in BGC823 cells transfected by shONECUT2. Similar results were observed in SST overexpression in MGC803 cells. Silencing ONECUT2 or overexpressing SST reduced the expressions of mesenchymal markers (N-cadherin and vimentin), STAT3, fibronectin, Wnt2, β-catenin and increased epithelial marker (E-cadherin), p-STAT3, smad2/3, α-catenin protein levels. In addition, inhibiting ONECUT2 or elevated SST suppressed tumor cell viability in vitro. Moreover, ONECUT2 silencing or elevated SST significantly inhibited tumor growth in vivo.

CONCLUSIONS: Up-regulated ONECUT2 and down-regulated SST promote gastric cell migration, invasion, epithelial-mesenchymal transition and tumor growth in gastric cancer.

 

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