miRNA Profiling in Cervical Cancer
L Kehoe, CD Spillane, M Gallagher, O Sheils, C Martin, JJ O'Leary. Trinity College Dublin, Dublin, Ireland; Coomne Womens and Infants University Hospital, Dublin, Ireland
Background: MicroRNAs (miRNA) have emerged as important molecules involved in cancer development. They are thus potential biomarkers and in the future may be developed as potential therapeutic targets.
Design: Using miRNA TaqMan low density arrays [TLDAs], we have profiled the expression of 377 miRNAs in cervical cancer (CC) cell lines. This data has been compared in two ways: comparison of CC cell lines to normal cervix and comparison of HPV positive to HPV negative cell lines. This approach allows the identification of CC and HPV specific miRNA expression patterns.
Results: Comparison of CC cell lines, HeLa, SiHa (HPV positive) and C33A (HPV negative) to normal cervix, has identified 87 miRNAs which are putative biomarkers of CC. The majority of miRNAs were found to be down regulated on comparison to normal cervix. Only one up regulated miRNA, common to all cell lines, was found: miR-301b. Top common down regulated miRNAs identified were: miR-133a, miR-139-3p, miR-145 and miR-223. Several of these have been described in cervical cancer (miR-145, miR-133a and miR-223) previously. Five miRNAs were found significantly dysregulated in HPV positive cell lines on comparison to normal cervix (miR-200a, miR-381, miR-493, miR-548b-5p and miR-146b-3p). miRNA expression was found to be associated with the presence of HPV 16 and 18, expanding our current understanding of miRNA regulation in CC. These can be grouped into miRNAs associated with HPV or those specific to HPV 16 or 18. 50 miRNAs were found to be common between the CC cell lines and therefore are putative biomarkers of CC. miR-548b-5p was found to down regulated in a HPV specific manner. Examination of common miRNAs revealed miR-335 and miR-214 to be the top up and down regulated miRNAs respectively. Further analysis revealed miR-335 may be up regulated in a HPV 18 specific manner. 33 miRNAs (28↑, 5↓) were associated with HPV 16 and 66 miRNAs (38↑, 28↓) with HPV 18. We have also identified that 16 miRNAs cluster to a 'hot-spot' miRNA region on chromosome 14, which appears to be associated with HPV 18 induced CC.
Conclusions: We have generated a list of miRNAs specific to CC and HPV 16 and/or 18 associated CC; thus providing a list of miRNAs for validation in CC material and also for target prediction analysis. This data may determine additional mechanisms of HPV induced cellular dysregulation and may also identify future therapeutic targets. We also describe a novel miRNA cluster on chromosome 14 in HPV 18 infected HeLa cells.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 191, Tuesday Morning