Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians

Marisa Shiina, Yutaka Hashimoto, Taku Kato, Soichiro Yamamura, Yuichiro Tanaka, Shahana Majid, Sharanjot Saini, Shahryari Varahram, Priyanka Kulkarni, Pritha Dasgupta, Yozo Mitsui, Mitsuho Sumida, Laura Tabatabai, Guoren Deng, Deepak Kumar, Rajvir Dahiya

Research output: Contribution to journalArticle

7 Scopus citations

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 (MDAPCA- 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 (MDAPCa- 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.

Original languageEnglish (US)
Pages (from-to)8356-8368
Number of pages13
JournalOncotarget
Volume8
Issue number5
DOIs
StatePublished - 2017

Keywords

  • African-Americans
  • Androgen receptor
  • Caucasians
  • Prostate cancer
  • miR-34b

ASJC Scopus subject areas

  • Oncology

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    Shiina, M., Hashimoto, Y., Kato, T., Yamamura, S., Tanaka, Y., Majid, S., Saini, S., Varahram, S., Kulkarni, P., Dasgupta, P., Mitsui, Y., Sumida, M., Tabatabai, L., Deng, G., Kumar, D., & Dahiya, R. (2017). Differential expression of miR-34b and androgen receptor pathway regulate prostate cancer aggressiveness between African-Americans and Caucasians. Oncotarget, 8(5), 8356-8368. https://doi.org/10.18632/oncotarget.14198