Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.
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 differe...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3790792?pdf=render |
| _version_ | 1811191599177138176 |
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| author | Zhi-Qiang Wang Mamadou Keita Magdalena Bachvarova Stephane Gobeil Chantale Morin Marie Plante Jean Gregoire Marie-Claude Renaud Alexandra Sebastianelli Xuan Bich Trinh Dimcho Bachvarov |
| author_facet | Zhi-Qiang Wang Mamadou Keita Magdalena Bachvarova Stephane Gobeil Chantale Morin Marie Plante Jean Gregoire Marie-Claude Renaud Alexandra Sebastianelli Xuan Bich Trinh Dimcho Bachvarov |
| author_sort | Zhi-Qiang Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T23:39:52Z |
| format | Article |
| id | doaj.art-28c0c58499314b859f8a8fff2c463be3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T23:39:52Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-28c0c58499314b859f8a8fff2c463be32022-12-22T03:56:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7438410.1371/journal.pone.0074384Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.Zhi-Qiang WangMamadou KeitaMagdalena BachvarovaStephane GobeilChantale MorinMarie PlanteJean GregoireMarie-Claude RenaudAlexandra SebastianelliXuan Bich TrinhDimcho BachvarovPreviously, 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.http://europepmc.org/articles/PMC3790792?pdf=render |
| spellingShingle | Zhi-Qiang Wang Mamadou Keita Magdalena Bachvarova Stephane Gobeil Chantale Morin Marie Plante Jean Gregoire Marie-Claude Renaud Alexandra Sebastianelli Xuan Bich Trinh Dimcho Bachvarov Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells. PLoS ONE |
| title | Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells. |
| title_full | Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells. |
| title_fullStr | Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells. |
| title_full_unstemmed | Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells. |
| title_short | Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells. |
| title_sort | inhibition of runx2 transcriptional activity blocks the proliferation migration and invasion of epithelial ovarian carcinoma cells |
| url | http://europepmc.org/articles/PMC3790792?pdf=render |
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