[Clinicopathological significance and function of miR-135b in the occurrence and development of gastric cancer].

OBJECTIVE: To explore the function and clinicopathological significance of miR-135b in the occurrence and development of gastric cancer.

METHODS: Seventy-two pairs of fresh gastric cancer tissues and corresponding normal gastric epithelium were collected at our department from September 2007 to March 2011. Six of them were randomly selected and miRNA microarray was applied to study the miRNA expression profiles of gastric cancer. Quantitative real-time PCR was used to validate the reliability of microarray and detect miR-135b expression in the above clinical samples, as well as cell lines GES-1, BGC-823 and SGC-7901. The methods of cell transfection, thiazolyl blue tetrazolium bromide (MTT) and flow cytometry were used to study the impact of miR-135 on cell proliferation, cell cycle and apoptosis of gastric cancer cells. Real-time quantitative PCR and Western blot were used to explore the relationship between miR-135b and adenomatous polyposis coli (APC).

RESULTS: Compared with normal gastric tissues, 7 miRNA were significantly up-regulated and 9 miRNA significantly down-regulated for over 2 folds in gastric cancer tissues (P < 0.05). The results of microarray were verified by quantitative real-time PCR. MiR-135b expression was up-regulated in most clinical samples compared with their corresponding epithelium (n = 66, 91.67%). The average expression level of miR-135b in gastric cancer tissues was significantly higher than normal epithelium (3.42 ± 2.62 vs 1.00 ± 0.07, P < 0.05). MiR-135b was related to Laurén classification, tumor differentiation, invasion and pathologic tumor-node-metastasis (pTNM) stage of gastric cancer (all P < 0.05). The worse differentiation degree of gastric cell lines, the higher miR-135b expression level (P < 0.05). MiR-135b promoted gastric cancer cell proliferation, inhibited its apoptosis and directly regulated the expression of APC in gastric cancer cell.

CONCLUSIONS: Special miRNA expression profiles of gastric cancer are found. MiR-135b is closely correlated with the biological behavior of human gastric cancer. And its regulation of APC may be one of the pathogenic mechanisms of gastric cancer.