Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians
Copyright policy )Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians
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.
- UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- University of the District of Columbia United States
- University of California, San Francisco United States
Male, Aging, Time Factors, Apoptosis, Androgen, androgen receptor, Receptors, 2.1 Biological and endogenous factors, Aetiology, Promoter Regions, Genetic, Cancer, African Americans, Tumor, Prostate Cancer, prostate cancer, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, african-americans, Receptors, Androgen, Chromosome Deletion, miR-34b, Research Paper, Signal Transduction, Urologic Diseases, 570, Clinical Sciences, Oncology and Carcinogenesis, 610, caucasians, Transfection, White People, Cell Line, Promoter Regions, Genetic, Cell Line, Tumor, Genetics, Humans, Cell Proliferation, Neoplastic, Biomedical and Clinical Sciences, Whites, Prostatic Neoplasms, Oncology and carcinogenesis, DNA Methylation, G1 Phase Cell Cycle Checkpoints, Black or African American, MicroRNAs, Gene Expression Regulation, Transcription Factors
Male, Aging, Time Factors, Apoptosis, Androgen, androgen receptor, Receptors, 2.1 Biological and endogenous factors, Aetiology, Promoter Regions, Genetic, Cancer, African Americans, Tumor, Prostate Cancer, prostate cancer, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, african-americans, Receptors, Androgen, Chromosome Deletion, miR-34b, Research Paper, Signal Transduction, Urologic Diseases, 570, Clinical Sciences, Oncology and Carcinogenesis, 610, caucasians, Transfection, White People, Cell Line, Promoter Regions, Genetic, Cell Line, Tumor, Genetics, Humans, Cell Proliferation, Neoplastic, Biomedical and Clinical Sciences, Whites, Prostatic Neoplasms, Oncology and carcinogenesis, DNA Methylation, G1 Phase Cell Cycle Checkpoints, Black or African American, MicroRNAs, Gene Expression Regulation, Transcription Factors
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