407000

MIR218-1

MIRN218-1|mir-218-1;microRNA 218-1;MIR218-1;microRNA 218-1

-

4p15.31

miscRNA

Count: 2; Pubmed_search,Generif

Growing evidence suggests that microRNAs (miRNAs) are aberrantly expressed in many human cancers, and that they play significant roles in carcinogenesis and cancer progression. The identification of tumor suppressive miRNAs and their target genes could provide new insights into the mechanism of carcinogenesis. However, the genetic or epigenetic regulations of these miRNAs have not yet been fully elucidated in bladder cancer (BC). Chromosomal alterations of cancer cells give us important information for the identification of tumor suppressor genes. Our miRNA array-comparative genomic hybridization (CGH) analysis showed several miRNAs to be candidate tumor suppressors of BC. Our array-CGH analysis revealed that chromosome 4 was lost in all BC cell lines. We selected 19 miRNAs located on chromosome 4 and evaluated their expression levels in cancer cell lines as well as clinical samples. Gain-of-function analysis revealed that miR-218 inhibited BC cell proliferation, migration and invasion. Furthermore, flow cytometry analysis showed that it induced BC cell apoptosis. Genome-wide gene expression analysis showed that it targeted multiple oncogenes in BC. Our study is the first to demonstrate that miR-218 located on chrosomosme 4p15.31 is a tumor suppressive miRNA in BC. The identification of tumor suppressive miRNAs and their target genes on the basis of array-CGH analysis could provide new insights into the mechanisms of BC carcinogenesis.

OBJECTIVE: To investigate the expression and function of miR-218 in gastric cancer. METHODS: miR-218 levels were evaluated in 20 non-cardia gastric cancer tissues using TaqMan stem-loop real-time PCR analysis. Pre-miR-218 and anti-miR-218 inhibitor were used to change the miR-218 expression level and examine its effects on cell proliferation, apoptosis, cell cycle and cell invasion. RESULTS: Comparing with the corresponding normal tissues, miR-218 expression was significantly reduced in the gastric cancer tissue (P < 0.01). Forced expression of miR-218 increased apoptosis in AGS cells. The proportion of apoptosis cells induced by transfection of pre-miR-218 was greater than that induced by control (21.6% vs. 10.4%, P = 0.032). Pre-miR-218 resulted in a significantly decreased cell growth activity (P < 0.01) and cell invasion (P < 0.05) of AGS cells compared with that of the control. CONCLUSION: miR-218 expression is reduced in gastric cancer. miR-218 may function as a tumor suppressor in gastric carcinoma.