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MicroRNAs (miRNAs) regulate gene expression by means of translational inhibition and mRNA degradation.They are abundant, highly conserved, and predicted to regulate a large number of transcripts in human. MiRNAs are also important for tumorigenesis, in particular hsa-miR-21 has been showed to inhibit apoptosis in breast and lung cancer. Over 450 miRNAs have been known in human, and many are associated with cell proliferation and differentiation. Using real-time quantitative PCR, we have identified a cluster of microRNAs at chromosome 7q32 being aberrantly up-regulated in cervical cancer cell lines compared with microdissected normal cervix epithelium. The up-regulation of this miRNA group is confirmed in cervical carcinoma tissues (n=22) compared with normal cervix epithelium (n=9, p<0.005). Using Agilent 44K human genome CGH array, we found that there was no structural variation in chromosome 7q32. This suggests that the miRNA expression may not be associated with the genomic copy number changes as suggested in breast and ovarian cancer. We have knocked down one of the aberrantly up-regulated microRNAs (hsa-miR-182) by siRNA with an efficiency of over 80% in 4 cervical cancer cell lines (ME180, CC3, SiHa and Hela). Further analysis by flow cytometry showed that the inhibition of hsa-miR-182 has no effect on cell cycle. Our data provide evidence and suggest that abnormal expression of miRNAs is implicated in tumorigenesis of cervical carcinoma. In addition, our aCGH results excluded chromosomal abnormalities as a major cause of disturbed miRNAs expression in cervical cancer. Currently, we are using the RNAi knock down approach to identify the potential target gene(s) for hsa-miR-182 in cervical cancer cell lines.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA