title: The RUNX1 transcription factor is expressed in serous epithelial ovarian carcinoma and contributes to cell proliferation, migration and invasion.
abstract: Previously, we have identified the RUNX1 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from epithelial ovarian cancer (EOC) patients, when compared with primary cultures derived from matched primary (prior to CT) tumors. Here we show that RUNX1 displays a trend of hypomethylation, although not significant, in omental metastases compared with primary EOC tumors. Surprisingly, RUNX1 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. The RUNX1 expression levels were almost identical in primary tumors and omental metastases, suggesting that RUNX1 hypomethylation might have a limited impact on its overexpression in advanced (metastatic) stage of the disease. Knockdown of the RUNX1 expression in EOC cells led to sharp decrease of cell proliferation and induced G 1 cell cycle arrest. Moreover, RUNX1 suppression significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX1 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 RUNX1 gene in EOC progression and suggest that RUNX1 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX1 and other members of the RUNX gene family in ovarian tumorigenesis.
authors: Department of Molecular Medicine, Laval University, Québec, QC, Canada.
authors: Mamadou
authors: M
authors: Keita
authors: Magdalena
authors: M
authors: Bachvarova
authors: Chantale
authors: C
authors: Morin
authors: Marie
authors: M
authors: Plante
authors: Jean
authors: J
authors: Gregoire
authors: Marie-Claude
authors: MC
authors: Renaud
authors: Alexandra
authors: A
authors: Sebastianelli
authors: Xuan Bich
authors: XB
authors: Trinh
authors: Dimcho
authors: D
authors: Bachvarov
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D008745:Methylation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D034741:RNA, Small Interfering; C493728:RUNX1 protein, human
keywords: Agilent Whole Human Genome Microarray; DNA hypomethylation; G1 cell cycle arrest; RUNX1; cell invasion; cell migration; cell proliferation; global gene expression; metastasis; ovarian cancer