MicroRNAs Expression Profiles Of Different Growth Patterns Of Gastric Cancer And Significance Of MiR-29c In Gastric Cancer

MicroRNAs are a class of single-stranded endogenous noncoding small RNAs, 22 nucleotides in length,which inhibits mRNA translation or directly degradate the target mRNA through its completely or not completely bonding to 3'-UTR.They produce post-transcriptional gene silencing, regulate gene expression, and play an important role in the proliferation, differentiation, apoptosis, gene regulation of cells and tumorigenesis. Different growth patterns of gastric cancer (Ming's expanding type and infiltrative type) show distinct biological behavior and clinical prognosis. There is important theoretical and practical significance about research on regulatory mechanism of growth patterns of gastric cancer. Series of evidence suggest that the growth patterns of gastric cancer may be regulated by microRNAs.In this study, 64 cases surgically resected gastric cancer were collected , include gastric cancer tissues and corresponding normal gastric epithelium from September 2007 to March 2011 in the first hosipital of Xiamen.After HE staining, three cases of expanding type and three cases of infiltrative type of gastric cancer tissues and corresponding normal gastric epithelium were select to detect microRNAs expression profiles by microRNA microarray. According to the results of microRNAs microarray, miR-29c were choosed as the research object, which was the most obvious downregulatd in Ming's infiltrative type gastric cancer. The reliability of microarray chips were validated by quantitative real-time PCR. Real-time PCR method was applied to detect miR-29c expression levels in gastric cancer and the corresponding normal epithelium, the normal gastric epithelium cell line GES-1 or gastric cancer cell lines SGC-7901 and BGC-823, followed by analysis of clinicopathological significance of miR-29c expression in gastric tissues and cell lines.MiRanda data bank was used to predict target genes of miR-29c and antiapoptotic Mcl-1 gene which showed good targeted relationshiop was picked up as research object. Mcl-1 mRNA were examined by quantitative real-time PCR detection in different growth patterns of gastic cancer. Influence of miR-29c on Mcl-1 mRNA expression level was observed by elevation of miR-29c in gastric cancer cell lines. Results shows that different microRNAs expression profiles were found inMing's expanding type and infiltrative type of gastric cancer. The reliability of microarray chips were verified by quantitative real-time PCR. Expression level of miR-29c was significantly lower than the corresponding normal gastric epithelium. Its expression level diminished in GES-1, SGC-7901 and BGC-823 in order, the worse differentiation , the lower its expression in cell lines. In gastric tissues, the expression level of miR-29c was significantly higher in the larger tumors (≥7cm),more number of lymphnode metastasis (N2 + N3),earlier the clinical stages (phaseⅢandⅣ),intestinal type of Laurén's classification,typeⅠa ndⅡof Borrmann's classification and expanding type of Ming's classification comparing with smaller tumors (< 7cm),less number of lymphnode metastasis (N0 + N1),earlier the clinical stages (phase I andⅡ),diffuse type of Laurén's classification,typeⅢandⅣof Borrmann's classification and inflirtative type of Ming's classification, respectively.Expression level of Mcl-1 mRNA was significantly higher than the corresponding normal gastric epithelium. Expression level of Mcl-1 mRNA significantly higher in expanding type than infiltrative type gastric cancer tissues. Expression of miR-29c and Mcl-1 is negatively related in gastric cancer. Mcl-1 mRNA expression can be significantly cuted down by elevation of miR-29c in gastric cancer cell lines.