Upregulation of miR-141 Potentially Limits Expression of JAG1 in Epithelial Ovarian Neoplasia
Lisa Keogh, Paul Smyth, John O'Leary, Orla Sheils, Richard Flavin. St. James's Hospital and Trinity College Dublin, Dublin, Ireland
Background: Ovarian cancer is the fifth most common cancer in women and has the highest mortality amongst gynecological cancers. This is largely due to the fact that ovarian cancer is difficult to detect at early stages. Each histological subtype of epithelial ovarian cancer has a distinct set of molecular characteristics making it difficult to pinpoint one set of molecular biomarkers that maybe used as diagnostic aids. MicroRNAs are small non-coding molecules that have been associated with the virtually all cancers. The miR-200 family which includes miR-141 has been linked to the Notch Signaling pathway, of which Jagged1, the protein product of JAG1 is part. JAG1 has been shown to have decreased expression in ovarian neoplasia due to a variety of reasons including changes in WNT signaling and knockdown of Notch3.
Design: FFPE blocks from normal ovary, benign and malignant mucinous and serous ovarian neoplasia (n=327) dating from 2005-2009 were retrieved from the archives of St. James Hospital and were microscopically reviewed for confirmation of diagnosis. 10µm sections were cut, H&E stained and laser capture microdissected to collect homogenous cell populations for subsequent analysis. RNA was subsequently extracted and reverse transcribed to cDNA. TaqMan-PCR was carried out on the cDNA, targeting miR-141 and JAG1. n=294 microRNA samples and n=250 gene samples were successfully amplified.
Results: miR-141 expression was consistently upregulated in disease cohorts relative to normal ovarian epithelium, whilst JAG1 was down-regulated across cohorts relative to normal ovarian epithelium. The two exceptions were a slight down-regulation of miR-141 in mixed benign ovarian neoplasias, and a slight upregulation of JAG1 in benign serous neoplasias.
Conclusions: miR-141 displays a reciprocal expression profile with JAG1. This suggests a regulatory role for miR-141 in ovarian cancer disease progression linking it with JAG1. miR-141 may be a potential therapeutic target for si-RNA intervention ameliorating aberrant Wnt signalling and restoring cellular equilibrium.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 191, Wednesday Afternoon