Xi'an Jiaotong University College of Medicine, Yanta Western Road 76, Xi'an 710061, China.
Mol Cancer Res. 2014 Mar;12(3):313-21. doi: 10.1158/1541-7786.MCR-13-0507. Epub 2013 Dec 27.
Results from recent studies suggest that aberrant microRNA expression is common in numerous cancers. Although miR-338-3p has been implicated in hepatocellular carcinoma, its role in gastric cancer is unknown. To this end, we report that miR-338-3p is downregulated in both gastric cancer tissue and cell lines. Forced expression of miR-338-3p inhibited cell proliferation and clonogenicity and induced a G1-S arrest as well as apoptosis in gastric cancer cells. Furthermore, P-Rex2a (PREX2) was identified as a direct target of miR-338-3p, and silencing P-Rex2a resulted in the same biologic effects of miR-338-3p expression in gastric cancer cells. Furthermore, both enforced expression of miR-338-3p or silencing of P-Rex2a resulted in activation of PTEN, leading to a decline in AKT phosphorylation. Also, miR-338-3p markedly inhibited the in vivo tumorigenicity in a nude mouse xenograft model system. These results demonstrate that miR-338-3p affects gastric cancer progression through PTEN-AKT signaling by targeting P-Rex2a in gastric cancer cells, which posits miR-338-3p as a novel strategy for gastric cancer treatment.
miR-338-3p acts as a novel tumor suppressor that blocks the growth of gastric cancer cells through PTEN-PI3K signaling by targeting P-Rex2a.
最近的研究结果表明，异常的 microRNA 表达在许多癌症中很常见。虽然 miR-338-3p 已被牵连到肝癌中，但它在胃癌中的作用尚不清楚。为此，我们报告 miR-338-3p 在胃癌组织和细胞系中均下调。miR-338-3p 的强制表达抑制了胃癌细胞的增殖和克隆形成，并诱导了 G1-S 期阻滞和细胞凋亡。此外，P-Rex2a（PREX2）被鉴定为 miR-338-3p 的直接靶标，沉默 P-Rex2a 导致胃癌细胞中 miR-338-3p 表达的相同生物学效应。此外，miR-338-3p 的强制表达或 P-Rex2a 的沉默均导致 PTEN 的激活，导致 AKT 磷酸化水平下降。同样，miR-338-3p 在裸鼠异种移植模型系统中显著抑制体内致瘤性。这些结果表明，miR-338-3p 通过靶向胃癌细胞中的 P-Rex2a 影响胃癌进展通过 PTEN-AKT 信号通路，这表明 miR-338-3p 是治疗胃癌的一种新策略。
miR-338-3p 作为一种新型肿瘤抑制因子，通过靶向 P-Rex2a 阻断胃癌细胞的生长，通过 PTEN-PI3K 信号通路发挥作用。
