Microrna Expression Profiling In Gastric Adenocarcinoma And Regulation Of Some Dysregulative Microrna On Gastric Cancer Cells

ObjectiveGastric adenocarcinoma is a very complex genetic disease characterized by alterations in oncogene and tumor-suppressor. More and more evidence indicates that microRNA, small non-protein-coding RNAs, might also function as tumor suppressors and oncogenes by regulating their target genes. However, the role of microRNA is still unclear in the initiation and progression of gastric adenocarcinoma. The aim of this study is to find the different microRNA expression between gastric adenocarcinoma and normal gastric tissue, and the function of dysregulative microRNA in gastric adenocarcinoma.Methods1 The different microRNA expression between 4 pairs of gastric adenocarcinoma and normal gastric tissue were detected by microRNA microarray. The results of microarray were analysed using hierarchical clustering and ratio analysis, and parts of the results were confirmed through semi-quantitative PCR.2 The effect of dysregulative microRNA on the proliferation of MGC803 was tested by MTT and colony formation assay.3 The targets of dysregulative microRNAs were predicted by bioinformation method, and confirmed by EGFP report system.Results1 Compared with normal tissue, several microRNAs are dysregulative expressed in gastric adenocarcinoma. We found that 13 microRNAs were up-regulated in gastric adenocarcinoma, whereas 9 microRNAs were down-regulated. Among them, up-regulation of miR-23a, miR-27a, miR-191 and down-regulation of miR-181b, miR-182, miR-210 were confirmed by semi- quantitative PCR.2 miR-181b, miR-182 had an antiproliferative effect on MGC803.3 CREB1 was predicted as a candidate target of both miR-181b and miR-182, and was confirmed by EGFP report system. ConclusionIn this study we report the different microRNA expression between gastric adenocarcinoma and normal gastric tissue, and found that miR-181b and miR-182 might function as a tumor suppressor by targeting an oncogene CREB1. All these results may be useful for the diagnosis, prognosis of gastric adenocarcinoma, and developing a new molecular targeted-therapy for this disease.