Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China.
Ann Surg Oncol. 2012 Jul;19 Suppl 3:S509-17. doi: 10.1245/s10434-011-1999-2. Epub 2011 Aug 16.
MiR-194 has been shown to be specifically expressed in the human gastrointestinal tract and may play an antimetastatic role in primary liver cancer cells. However, the role of miR-194 in gastric cancer is still unclear.
Total RNA was extracted from tissues of 119 patients with gastric cancer and three gastric cancer cell lines (SGC-7901, MGC-803, and BGC-823). Expression levels of miR-194 were determined by real-time polymerase chain reaction (PCR). Moreover, a MTT proliferation assay and transwell cell invasion assay were performed to study the effect of miR-194 on SGC-7901 cell proliferation and invasion. Finally, we used real-time PCR and western blot to verify which gene was the target of miR-194 in gastric cancer.
Though there was no significant difference between cancerous and matching noncancerous tissues, we found patients with lower expression of miR-194 tended to have larger tumor size (P = 0.002) and more advanced pT stage (P = 0.028) in gastric cancer. Moreover, the expression of miR-194 was significantly lower in Borrmann IV type gastric cancer than in Borrmann I, II, and III types (P = 0.019). Furthermore, an in vitro invasion assay indicated that the penetrated cell intensity after miR-194 mimics transfection was significantly lower than the control. However, overexpression of miR-194 had little effect on the SGC-7901 cell cycle and proliferation. The results of real-time PCR and western blot highlighted that miR-194 interacted with N-cadherin and negatively regulated its expression at the translational level.
These findings imply that miR-194 might play an important role in gastric cancer invasion and progression.
miR-194 特异性表达于人类胃肠道,可能在原发性肝癌细胞中发挥抗转移作用。然而,miR-194 在胃癌中的作用尚不清楚。
从 119 例胃癌患者的组织和三种胃癌细胞系(SGC-7901、MGC-803 和 BGC-823)中提取总 RNA。采用实时聚合酶链反应(PCR)检测 miR-194 的表达水平。此外,采用 MTT 增殖实验和 Transwell 细胞侵袭实验研究 miR-194 对 SGC-7901 细胞增殖和侵袭的影响。最后,我们采用实时 PCR 和 Western blot 验证了 miR-194 在胃癌中的靶基因。
尽管癌组织与配对的非癌组织之间没有显著差异,但我们发现 miR-194 低表达的患者胃癌肿瘤体积较大(P = 0.002),pT 分期较高(P = 0.028)。此外,Borrmann IV 型胃癌 miR-194 的表达明显低于 Borrmann I、II 和 III 型(P = 0.019)。此外,体外侵袭实验表明,miR-194 模拟物转染后穿透细胞的强度明显低于对照组。然而,miR-194 的过表达对 SGC-7901 细胞周期和增殖几乎没有影响。实时 PCR 和 Western blot 的结果表明,miR-194 与 N-钙黏蛋白相互作用,并在翻译水平上负调控其表达。
这些发现表明,miR-194 可能在胃癌侵袭和进展中发挥重要作用。