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Kaiso, a transcriptional repressor, promotes cell migration and invasion of prostate cancer cells through regulation of miR-31 expression

Honghe Wang, Wei Liu, ShaNekkia Black, Omari Turner, Juliet M. Daniel, Windy Dean-Colomb, Qinghua P. He, Melissa Davis and Clayton Yates _

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Oncotarget. 2016; 7:5677-5689. https://doi.org/10.18632/oncotarget.6801

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Abstract

Honghe Wang1, Wei Liu2, ShaNekkia Black1, Omari Turner1, Juliet M. Daniel5, Windy Dean-Colomb6, Qinghua P. He3, Melissa Davis4, Clayton Yates1

1Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, USA

2Laboratory of Comparative Carcinogenesis, Cancer Center of Research, Frederick, MD, USA

3Department of Chemical Engineering, Tuskegee University, Tuskegee, AL, USA

4Department of Genetics, University of Georgia, Athens, GA, USA

5Department of Biology, McMaster University, Hamilton, ON, Canada

6Department of Oncologic Research, University Hospital and Clinics, Lafayette General Health, Lafayette, LA, USA

Correspondence to:

Clayton Yates, e-mail: cyates@mytu.tuskegee.edu

Keywords: miRNA, Kaiso, DNA methylation, prostate cancer

Received: July 10, 2015     Accepted: December 09, 2015     Published: December 30, 2015

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.


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