Rab1A, a member of the Ras-like protein in rat brain (Rab) family, acts as an oncogene in a variety of malignant tumors. Previous studies reported that Rab1A was highly expressed in GC tissues. However, the function and molecular mechanism of Rab1A in gastric cancer (GC) development remain far from being addressed. Rab1A mRNA and protein levels were detected by qRT-PCR and western blot, respectively. Cell proliferation was evaluated by CCK-8 and BrdU incorporation assays. Apoptosis was estimated by flow cytometry analysis and western blot analysis of B cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), Bcl-2 associated X (Bax), and Bcl-2 homologous antagonist/killer (Bak) expression. Alteration of the mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling pathway was detected by western blot. We found that Rab1A expression at both mRNA and protein was upregulated in GC cells. Rab1A knockdown significantly inhibited cell proliferation and induced apoptosis in GC cells. Rab1A overexpression promoted proliferation, inhibited cisplatin-induced apoptosis, and increased xenograft growth. In addition, we found that Rab1A knockdown suppressed the mTOR/p70S6K pathway in GC cells. Moreover, activation of mTOR/p70S6K pathway by MHY1485 abolished the effects of Rab1A knockdown on cell proliferation and apoptosis. In conclusion, Rab1A knockdown repressed proliferation and promoted apoptosis in GC cells by inhibition of the mTOR/p70S6K pathway.

中文翻译：

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Rab1A组合式抑制mTOR / p70S6K途径抑制胃癌细胞的增殖并促进其凋亡。

Rab1A是大鼠脑（Rab）家族中Ras样蛋白的成员，在多种恶性肿瘤中起癌基因的作用。先前的研究报告说Rab1A在GC组织中高度表达。然而，Rab1A在胃癌（GC）发育中的功能和分子机制仍未得到解决。通过qRT-PCR和western blot分别检测Rab1A mRNA和蛋白水平。通过CCK-8和BrdU掺入测定法评估细胞增殖。B细胞淋巴瘤2（Bcl-2），髓样细胞白血病1（Mcl-1），Bcl-2相关X（Bax）和Bcl-2同源拮抗剂/杀伤剂（ Bak）表达。通过蛋白质印迹法检测了哺乳动物雷帕霉素（mTOR）/ p70核糖体蛋白S6激酶（p70S6K）信号通路的靶标的改变。我们发现Rab1A在mRNA和蛋白质上的表达在GC细胞中均被上调。Rab1A基因敲低显着抑制细胞增殖，并诱导GC细胞凋亡。Rab1A过表达促进增殖，抑制顺铂诱导的细胞凋亡，并增加异种移植物的生长。此外，我们发现Rab1A抑制可抑制GC细胞中的mTOR / p70S6K途径。此外，MHY1485对mTOR / p70S6K通路的激活消除了Rab1A抑制对细胞增殖和凋亡的影响。总之，Rab1A抑制通过抑制mTOR / p70S6K途径抑制GC细胞的增殖并促进其凋亡。抑制顺铂诱导的细胞凋亡，并增加异种移植物的生长。此外，我们发现Rab1A抑制可抑制GC细胞中的mTOR / p70S6K途径。此外，MHY1485对mTOR / p70S6K通路的激活消除了Rab1A抑制对细胞增殖和凋亡的影响。总之，Rab1A抑制通过抑制mTOR / p70S6K途径抑制GC细胞的增殖并促进其凋亡。抑制顺铂诱导的细胞凋亡，并增加异种移植物的生长。此外，我们发现Rab1A敲低抑制了GC细胞中的mTOR / p70S6K途径。此外，MHY1485对mTOR / p70S6K通路的激活消除了Rab1A抑制对细胞增殖和凋亡的影响。总之，Rab1A抑制通过抑制mTOR / p70S6K途径抑制GC细胞的增殖并促进其凋亡。