MiR-۴۹۳ suppresses the proliferation and invasion of gastric cancer cells by targeting RhoC

Objective(s):MiRNAs have been proposed to be key regulators of tumorigenesis, progression and metastasis. However, their effect and prognostic value in gastric cancer is still poorly known. Materials and Methods: Gastric cancer cell lines were cultured. Tissue samples obtained from ۳۶ gastric cancer patients were used for quantitative real-time PCR (qRT-PCR) analysis. The tissue microarrays (TMAs) consisted of ۱۲۶ cases of gastric carcinoma that were used for In situ hybridisation (ISH). Lentivirus plasmids were co-transfected into ۲۹۳FT cells. Cell migration was examined using wound-healing assays. Statistical analyses were performed using SPSS۱۶.۰ software. Results: In this study, we found that the expression levels of miR-۴۹۳ were strongly down-regulated in gastric cancer and were associated with clinical stage and the presence of lymph node metastases. Moreover, miR-۴۹۳ might independently predict OS and RFS in gastric cancer. We further found that up-regulation of miR-۴۹۳ inhibited the proliferation and metastasis of gastric cancer cells, in vitro and in vivo. In addition, miR-۴۹۳ directly targeted RhoC, which resulted in a marked reduction of the expression of mRNA and protein. This effect, in turn, led to a decreased ability of growth, invasion and metastasis in gastric cancer cells. Conclusion: Taken together, our findings demonstrate that miR-۴۹۳ is important for gastric cancer initiation and progression and holds promise as a prognostic biomarker to predict survival and relapse in gastric cancer. It is also a potential therapeutic tool to improve clinical outcomes in this disease.

Keywords:

Gastric cancer , miR-۴۹۳ , Proliferation , Invasion , Prognostic significance