ARID3B directly regulates ovarian cancer promoting genes

Alexander Bobbs, Katrina Gellerman, William Morgan Hallas, Stancy Joseph, Chao Yang, Jeffrey Kurkewich, Karen Cowden Dahl

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The DNA-binding protein AT-Rich Interactive Domain 3B (ARID3B) is elevated in ovarian cancer and increases tumor growth in a xenograft model of ovarian cancer. However, relatively little is known about ARID3B's function. In this study we perform the first genome wide screen for ARID3B direct target genes and ARID3B regulated pathways. We identified and confirmed numerous ARID3B target genes by chromatin immunoprecipitation (ChIP) followed by microarray and quantitative RT-PCR. Using motif-finding algorithms, we characterized a binding site for ARID3B, which is similar to the previously known site for the ARID3B paralogue ARID3A. Functionality of this predicted site was demonstrated by ChIP analysis. We next demonstrated that ARID3B induces expression of its targets in ovarian cancer cell lines. We validated that ARID3B binds to an epidermal growth factor receptor (EGFR) enhancer and increases mRNA expression. ARID3B also binds to the promoter of Wnt5A and its receptor FZD5. FZD5 is highly expressed in ovarian cancer cell lines, and is upregulated by exogenous ARID3B. Both ARID3B and FZD5 expression increase adhesion to extracellular matrix (ECM) components including collagen IV, fibronectin and vitronectin. ARID3B-increased adhesion to collagens II and IV require FZD5. This study directly demonstrates that ARID3B binds target genes in a sequence-specific manner, resulting in increased gene expression. Furthermore, our data indicate that ARID3B regulation of direct target genes in the Wnt pathway promotes adhesion of ovarian cancer cells.

Original languageEnglish (US)
Article numbere0131961
JournalPLoS One
Volume10
Issue number6
DOIs
StatePublished - Jun 29 2015

Fingerprint

ovarian neoplasms
Neoplasm Genes
Ovarian Neoplasms
Genes
adhesion
Adhesion
Chromatin Immunoprecipitation
Cells
genes
Chromatin
chromatin
collagen
Collagen
cell lines
Vitronectin
Cell Line
Wnt Signaling Pathway
DNA-binding proteins
fibronectins
DNA-Binding Proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bobbs, A., Gellerman, K., Hallas, W. M., Joseph, S., Yang, C., Kurkewich, J., & Cowden Dahl, K. (2015). ARID3B directly regulates ovarian cancer promoting genes. PLoS One, 10(6), [e0131961]. https://doi.org/10.1371/journal.pone.0131961

ARID3B directly regulates ovarian cancer promoting genes. / Bobbs, Alexander; Gellerman, Katrina; Hallas, William Morgan; Joseph, Stancy; Yang, Chao; Kurkewich, Jeffrey; Cowden Dahl, Karen.

In: PLoS One, Vol. 10, No. 6, e0131961, 29.06.2015.

Research output: Contribution to journalArticle

Bobbs, A, Gellerman, K, Hallas, WM, Joseph, S, Yang, C, Kurkewich, J & Cowden Dahl, K 2015, 'ARID3B directly regulates ovarian cancer promoting genes', PLoS One, vol. 10, no. 6, e0131961. https://doi.org/10.1371/journal.pone.0131961
Bobbs A, Gellerman K, Hallas WM, Joseph S, Yang C, Kurkewich J et al. ARID3B directly regulates ovarian cancer promoting genes. PLoS One. 2015 Jun 29;10(6). e0131961. https://doi.org/10.1371/journal.pone.0131961
Bobbs, Alexander ; Gellerman, Katrina ; Hallas, William Morgan ; Joseph, Stancy ; Yang, Chao ; Kurkewich, Jeffrey ; Cowden Dahl, Karen. / ARID3B directly regulates ovarian cancer promoting genes. In: PLoS One. 2015 ; Vol. 10, No. 6.
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