The epidermal growth factor receptor responsive miR-125a represses mesenchymal morphology in ovarian cancer cells.
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 from a mesenchymal to an epithelial morphology, 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.
Cowden Dahl
Karen D
KD
Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131-0001, USA. kcowdendahl@salud.unm.edu
Dahl
Richard
R
Kruichak
Jessica N
JN
Hudson
Laurie G
LG
D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008648:Mesoderm; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C120893:ARID3B protein, human; D004268:DNA-Binding Proteins; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C065788:transcription factor PEA3; D066246:ErbB Receptors