title: Kaiso, a transcriptional repressor, promotes cell migration and invasion of prostate cancer cells through regulation of miR-31 expression.
abstract: Kaiso, a member of the BTB/POZ zinc finger protein family, functions as a transcriptional repressor by binding to sequence-specific Kaiso binding sites or to methyl-CpG dinucleotides. Previously, we demonstrated that Kaiso overexpression and nuclear localization correlated with the progression of prostate cancer (PCa). Therefore, our objective was to explore the molecular mechanisms underlying Kaiso-mediated PCa progression. Comparative analysis of miRNA arrays revealed that 13 miRNAs were significantly altered (> 1.5 fold, p < 0.05) in sh-Kaiso PC-3 compared to sh-Scr control cells. Real-time PCR validated that three miRNAs (9, 31, 636) were increased in sh-Kaiso cells similar to cells treated with 5-aza-2'-deoxycytidine. miR-31 expression negatively correlated with Kaiso expression and with methylation of the miR-31 promoter in a panel of PCa cell lines. ChIP assays revealed that Kaiso binds directly to the miR-31 promoter in a methylation-dependent manner. Over-expression of miR-31 decreased cell proliferation, migration and invasiveness of PC-3 cells, whereas cells transfected with anti-miR-31 restored proliferation, migration and invasiveness of sh-Kaiso PC-3 cells. In PCa patients, Kaiso high/miR-31 low expression correlated with worse overall survival relative to each marker individually. In conclusion, these results demonstrate that Kaiso promotes cell migration and invasiveness through regulation of miR-31 expression.
authors.affiliation: Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, USA.
authors.forename: Honghe
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Comparative Carcinogenesis, Cancer Center of Research, Frederick, MD, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, USA.
authors.forename: ShaNekkia
authors.initials: S
authors.lastname: Black
authors.affiliation: Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, USA.
authors.forename: Omari
authors.initials: O
authors.lastname: Turner
authors.affiliation: Department of Biology, McMaster University, Hamilton, ON, Canada.
authors.forename: Juliet M
authors.initials: JM
authors.lastname: Daniel
authors.affiliation: Department of Oncologic Research, University Hospital and Clinics, Lafayette General Health, Lafayette, LA, USA.
authors.forename: Windy
authors.initials: W
authors.lastname: Dean-Colomb
authors.affiliation: Department of Chemical Engineering, Tuskegee University, Tuskegee, AL, USA.
authors.forename: Qinghua P
authors.initials: QP
authors.lastname: He
authors.affiliation: Department of Genetics, University of Georgia, Athens, GA, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Davis
authors.affiliation: Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, USA.
authors.forename: Clayton
authors.initials: C
authors.lastname: Yates
mesh_terms: D017209:Apoptosis; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; C492254:ZBTB33 protein, human
keywords: DNA methylation; Kaiso; miRNA; prostate cancer