Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region, P.R. China.
Eur Rev Med Pharmacol Sci. 2020 Sep;24(18):9378-9390. doi: 10.26355/eurrev_202009_23021.
Gastric cancer is a common malignancy, with high metastasis and poor prognosis. Our purpose was to explore potential molecular mechanisms of gastric cancer.
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.
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.
Up-regulated ONECUT2 and down-regulated SST promote gastric cell migration, invasion, epithelial-mesenchymal transition and tumor growth in gastric cancer.
胃癌是一种常见的恶性肿瘤，具有高转移和预后不良的特点。我们的目的是探索胃癌的潜在分子机制。
共收集了 10 对胃癌组织和相邻正常胃组织进行 RNA 测序（RNA-seq），然后进行差异表达分析。结合 qRT-PCR 结果，选择了两个新的基因进行深入分析，包括上调的 ONECUT 和下调的 SST。为了研究 ONECUT 和 SST 对胃癌细胞生物学行为的影响，使用 ONECUT2 敲低和 SST 过表达转染胃癌细胞系。随后，通过 Transwell 测定法检测细胞迁移和侵袭，通过 Western blot 分析测定上皮-间充质转化（EMT）相关蛋白的表达。此外，通过 CCK-8 测定法检测细胞活力。最后，在裸鼠中进行了肿瘤发生实验。
在 BGC823 细胞中转染 shONECUT2 抑制了胃癌细胞的迁移和侵袭。在 MGC803 细胞中转染 SST 过表达也观察到了类似的结果。沉默 ONECUT2 或过表达 SST 降低了间充质标志物（N-钙黏蛋白和波形蛋白）、STAT3、纤维连接蛋白、Wnt2、β-连环蛋白的表达，并增加了上皮标志物（E-钙黏蛋白）、p-STAT3、smad2/3、α-连环蛋白蛋白水平。此外，抑制 ONECUT2 或升高 SST 抑制了体外肿瘤细胞的活力。此外，ONECUT2 沉默或 SST 升高显著抑制了体内肿瘤的生长。
上调的 ONECUT2 和下调的 SST 促进了胃癌细胞的迁移、侵袭、上皮-间充质转化和肿瘤生长。
