title: Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.
abstract: Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from serous epithelial ovarian cancer (EOC) patients, when compared to primary cultures derived from matched primary (prior to CT) tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic) stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in serous EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis.
authors.affiliation: Department of Molecular Medicine, Laval University, Québec (Québec), Canada ; Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec (Québec), Canada.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Mamadou
authors.initials: M
authors.lastname: Keita
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bachvarova
authors.forename: Stephane
authors.initials: S
authors.lastname: Gobeil
authors.forename: Chantale
authors.initials: C
authors.lastname: Morin
authors.forename: Marie
authors.initials: M
authors.lastname: Plante
authors.forename: Jean
authors.initials: J
authors.lastname: Gregoire
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Renaud
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sebastianelli
authors.forename: Xuan Bich
authors.initials: XB
authors.lastname: Trinh
authors.forename: Dimcho
authors.initials: D
authors.lastname: Bachvarov
mesh_terms: D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit