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[947] MicroRNA Signatures in Cervical Cancer: Suggests Hierarchical miRNA Control of Gene Expression

CM Martin, K Astbury, C Becker, R Henfrey, J Sherlock, S Guenther, O Sheils, JJ O'Leary. Trinity College, Dublin, Ireland; Applied Biosystems Europe, Warrington, United Kingdom

Background: Cervical cancer, a potentially preventable disease, remains the second most common female malignancy worldwide. Human papilloma virus (HPV) has been implicated in the development of virtually all cases of cervical cancer. MicroRNAs (miRNAs) are a recently discovered family of small non-protein-coding RNAs known to negatively regulate expression of protein coding genes. Their expression profiles can be used for the classification, diagnosis, and prognosis of human malignancies.
Design: In this study, we examined the expression of 180 characterised miRNA molecules and carried out predicitive protein target analysis in cervical cancer cell lines: C33A (HPV negative), SiHA (HPV 16), CaSki (HPV 16 and 18) and normal cervical tissue using the Applied Biosystems TaqMan MicroRNA Assays Human Panel - Early Access Kit. Biological and technical replicate and serial passage analysis was carried out.
Results: C33A, SiHA and CaSki cells demonstrated distinct miRNA expression signatures in comparison with normal cervical tissue. In addition, differential miRNA expression patterns were observed between HPV positive and negative cell lines, with the predicted function of differentially expressed targets coinciding with a number of cell cycle regulatory molecules, including CDKN2a, CDK 6 and 8, Cyclin D2, Cdc14, p16, E2F and Rb. In particular CHEK 1, MYBL 2, cyclin E1 and E2 gene expression in cervical cancer appears to be selectively controlled by hierarchical miRNA species, suggesting master miRNA gene control in specific hierarchical miRNA expression cascades. Expression profiles of miRNAs demonstrated high stability and reproducibility in serial passage experiments.
Conclusions: These findings highlight the potential importance of miRNA in the complex pathobiology of cervical pre-cancer and cancer. These miRNAs may serve as potential biomarkers of pre-invasive cervical disease and potential therapeutic targets. In addition, the control of RNA and protein expression via miRNAs is highly regulated and hierarchical. The research team are members of the Irish Cervical Screening Research Consortium [ICSRC].
Category: Gynecologic

Wednesday, March 28, 2007

Poster # 119, Wednesday Morning