The epidermal growth factor receptor responsive miR-125a represses mesenchymal morphology in ovarian cancer cells

Karen D. Cowden Dahl, Richard Dahl, Jessica N. Kruichak, Laurie G. Hudson

Research output: Contribution to journalArticle

110 Scopus citations


The epithelial-to-mesenchymal transition (EMT) that occurs during embryonic development is recapitulated during tumor metastasis. Important regulators of this process include growth factors, transcription factors, and adhesion molecules. New evidence suggests that microRNA (miRNA) activity contributes to metastatic progression and EMT; however, the mechanisms leading to altered miRNA expression during cancer progression remain poorly understood. Importantly, overexpression of the epidermal growth factor receptor (EGFR) in ovarian cancer correlates with poor disease outcome and induces EMT in ovarian cancer cells.We report that EGFR signaling leads to transcriptional repression of the miRNA miR-125a through the ETS family transcription factor PEA3. Overexpression of miR-125a induces conversion of highly invasive ovarian cancer cells fromamesenchymal to an epithelialmorphology, suggesting miR-125a is a negative regulator of EMT. We identify AT-rich interactive domain 3B (ARID3B) as a target of miR-125a and demonstrate that ARID3B is overexpressed in human ovarian cancer. Repression of miR-125a through growth factor signaling represents a novel mechanism for regulating ovarian cancer invasive behavior.

Original languageEnglish (US)
Pages (from-to)1208-1215
Number of pages8
Issue number11
StatePublished - Nov 2009


ASJC Scopus subject areas

  • Cancer Research

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