title: MicroRNAs regulate KDM5 histone demethylases in breast cancer cells.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Alteration of miRNA levels is common in tumors and contributes to the pathogenesis of human malignancies. In the present study we examined the role played by miR-137 in breast tumorigenesis. We found miR-137 levels to be lower in breast cancer cells than in their non-tumorigenic counterparts and observed reduced proliferation and migration of breast cancer cells overexpressing miR-137. We further identified KDM5B, a histone demethylase known to be involved in breast cancer tumorigenesis, as a target of miR-137. As the involvement of histone demethylases in cancer is still poorly understood and as the role of miRNAs in controlling epigenetic mechanisms in cancer is emerging, we broadened our study to the whole KDM5 histone demethylase family to see if the genes coding for these epigenetic enzymes might be regulated by miRNAs in cancer cells. We discovered that KDM5C is overexpressed in breast cancer cells, providing evidence that miR-138 regulates its expression. We found miR-138 overexpression to affect breast cancer cell proliferation. Altogether, our findings suggest that miRNAs may regulate KDM5 histone demethylase levels in breast cancer and thereby control breast cancer cell proliferation and migration.
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. rdeplus@ulb.ac.be.
authors.forename: Hélène
authors.initials: H
authors.lastname: Denis
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. rdeplus@ulb.ac.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: Van Grembergen
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. rdeplus@ulb.ac.be.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Delatte
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. rdeplus@ulb.ac.be.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dedeurwaerder
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. rdeplus@ulb.ac.be.
authors.forename: Pascale
authors.initials: P
authors.lastname: Putmans
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. rdeplus@ulb.ac.be.
authors.forename: Emilie
authors.initials: E
authors.lastname: Calonne
authors.affiliation: Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Rothé
authors.affiliation: Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. rdeplus@ulb.ac.be.
authors.forename: François
authors.initials: F
authors.lastname: Fuks
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. rdeplus@ulb.ac.be.
authors.forename: Rachel
authors.initials: R
authors.lastname: Deplus
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004794:Enzyme Repression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C545567:MIRN137 microRNA, human; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012097:Repressor Proteins; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human; C086877:KDM5C protein, human