| Background: Gastric cancer(GC), one of the most common malignancy tumors, ranks the fifth common cancer and has the third highest mortality rate. In recent years, the incidence and mortality of gastric cancer have decreased worldwide, but it remains the leading cause of cancer-related deaths in developing countries. In the world, the incidence of gastric cancer in men is twice that of women. The incidence and mortality vary with areas. In China, gastric cancer ranks third, only after lung cancer and liver cancer. In the early stage of gastric cancer, there are no obvious symptoms, so the patients were diagnosed with advanced gastric cancer. Thus, they miss the best timing of treatment. With the development of science and technology, diagnostic tools and treatment programs become advanced, but the prognosis of patients with gastric cancer remains poor.Micro RNAs(miRNAs) are a class of endogenous non-coding small RNA. As we all known, the mi RNAs are involved in the biological regulation of tumor cells, and play an important role in the diagnosis and prognosis of tumors. Numerous studies reported that the mi RNAs is closely related with prognosis of a variety of malignancies, including gastric cancer. Therefore, screening the suitable mi RNAs has great clinical value as prognosis biomarkers for gastric cancer. In our previous study,we using Taq Man low density array to screen four mi RNAs which were down-regulated in plasma. In this study, we aimed to find mi RNAs as biomarkers for the prognosis of gastric cancer.Methods: We used the real-time polymerase chain reaction to detect the expression of four caculated mi RNAs(mi R-148 a, mi R-142-3p, mi R-26 a and mi R-195) in the paraffin-embedded surgical samples(the first stage: n=387; the second stage: n=169). We conducted a search in Pub Med and assessed survival in gastric cancer by mi RNAs. The Meta-analysis was performed by using STATA11.0. RT-PCR were used to detect the expression of mi RNA in MGC 803, BGC 823, SGC 7901 and MKN 28, the gastric cancer cell lines, and GES-1, the normal gastric mucosa cell line. After infected the gastric cancer cell line MGC 803 with mi RNA mimics, the cancer cell proliferation, migration, invasion and apoptosis were identified by cell counting kit-8(CCK-8), clonability assays, transwell cell assays and flow cytometer(FCM).Results: The low expression levels of mi R-26 a and mi R-148 a were associated with the poor survival either in the first stage or the second stage. We found that the expression level of mi R-26 a and mi R-148 a, the depth of invasion, lymph node Metastasis, TNM stage, and degree of differentiation are associated with poor prognosis. Multivariate Cox regression analysis revealed that mi R-26a/mi R-148 a could improve the overall survival of gastric cancer(mi R-26a: HR = 0.76, 95%CI = 0.61-0.94; mi R-148a: HR = 0.73, 95%CI = 0.58-0.91). It is also identified that TNM stage and chemotherapy were relative to the prognosis(P < 0.05).Because there are a number of studies about the effect of mi R-148 a in gastric cancer, our study focused on the expression and functions of mi R-26 a in the growth and development of gastric cancer. The level of mi R-26 a in MGC 803 cell was notable least than that in the normal GES-1 cell. Forty-eight hours after transfection with mi R-26 a, the abilities of gastric cancer cell proliferation, colony, migration andinvasion were significantly inhibited compared with negative control infection(P < 0.05). The result showed that the overexpression of mi R-26 a promotes apoptosis.Conclusions: mi R-26 a and mi R-148 a were decresed in gastric cancer, and the low expressions of mi R-26 a and mi R-148 a, TNM stage, the depth of invasion, lymph node Metastasis were significantly related with the overall survival. Moreover, mi R-26 a suppresses the growth and Metastasis of gastric cancer, and it could be used as a potential biomarker to predict the prognosis of patients with gastric cancer after surgery. |
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