title: Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians.
abstract: African-Americans are diagnosed with more aggressive prostate cancers and have worse survival than Caucasians, however a comprehensive understanding of this health disparity remains unclear. To clarify the mechanisms leading to this disparity, we analyzed the potential involvement of miR-34b expression in African-Americans and Caucasians. miR-34b functions as a tumor suppressor and has a multi-functional role, through regulation of cell proliferation, cell cycle and apoptosis. We found that miR-34b expression is lower in human prostate cancer tissues from African-Americans compared to Caucasians. DNA hypermethylation of the miR-34b-3p promoter region showed significantly higher methylation in prostate cancer compared to normal samples. We then sequenced the promoter region of miR-34b-3p and found a chromosomal deletion in miR-34b in African-American prostate cancer cell line (MDA-PCA-2b) and not in Caucasian cell line (DU-145). We found that AR and ETV1 genes are differentially expressed in MDA-PCa-2b and DU-145 cells after overexpression of miR-34b. Direct interaction of miR-34b with the 3' untranslated region of AR and ETV1 was validated by luciferase reporter assay. We found that miR-34b downregulation in African-Americans is inversely correlated with high AR levels that lead to increased cell proliferation. Overexpression of miR-34b in cell lines showed higher inhibition of cell proliferation, apoptosis and G1 arrest in the African-American cells (MDA-PCa-2b) compared to Caucasian cell line (DU-145). Taken together, our results show that differential expression of miR-34b and AR are associated with prostate cancer aggressiveness in African-Americans.
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Marisa
authors.initials: M
authors.lastname: Shiina
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Taku
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamamura
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Sharanjot
authors.initials: S
authors.lastname: Saini
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Shahryari
authors.initials: S
authors.lastname: Varahram
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Pritha
authors.initials: P
authors.lastname: Dasgupta
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Mitsui
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Mitsuho
authors.initials: M
authors.lastname: Sumida
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Tabatabai
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.affiliation: Division of Science and Mathematic, Cancer Research Laboratory, University of the District of Columbia, Washington, DC, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, San Francisco, California, USA.
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D001741:Black or African American / Q000235:genetics*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002872:Chromosome Deletion; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D044465:White People / Q000235:genetics*
chemical_list: C410798:AR protein, human; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D011944:Receptors, Androgen; D014157:Transcription Factors
keywords: african-americans; androgen receptor; caucasians; miR-34b; prostate cancer