Oncogenic and anti-oncogenic microRNAs in cell transformation

M (miRNAs) are an abundant class of small noncoding RNAs that function primarily as oncogenes and tumor suppressors by mediating translational repression or mRNA degradation via binding target genes. In this study, malignant human bronchial epithelial cells transformed by anti-benzo[a]pyrenetrans-7, 8-diol-9, 10-epoxide were used to help characterize the possible mechanisms of miRNA function in chemical carcinogenesis. The expression level of miRNAs was measured by microarray analysis and real time PCR. We used the specific miRNA inhibitors and mimics to down regulate or upregulate miRNA activity in malignantly transformed cells to determine the effects of miRNAs on the biological properties of the cell. Silencing miR-106a, miR-494 or miR-22 by transfection with the inhibitor suppressed cell proliferation, induced cell cycle arrest and apoptosis, and inhibited anchorage-independent growth and tumor growth in nude mice. Increasing the expression of miR106a, miR-494 or miR-22 in malignantly transformed cells by transfection with the mimic gave the opposite results. Bioinformatic analysis showed that tumor suppressor RB1 is one of predictive targets of miR-106a, and PTEN gene is a target of miR-494 and miR-22. We confirmed these targets by western blot and luciferase reporter assays. These findings suggest that miR-106a, miR494 and miR-22 might function as oncogenes in transformation induced by a chemical carcinogen. Our study on miR-506 revealed that miR-506 acts as an anti-oncogenic miRNA by regulating Ras in malignantly transformed cells. The identification of oncogenic and anti-oncogenic miRNAs could provide new insight into the molecular mechanisms of chemical carcinogenesis.