Upregulation of MIR-130b contributes to risk of poor prognosis and racial disparity in African-American Prostate Cancer

Yutaka Hashimoto, Marisa Shiina, Pritha Dasgupta, Priyanka Kulkarni, Taku Kato, Ryan K. Wong, Yuichiro Tanaka, Varahram Shahryari, Shigekatsu Maekawa, Soichiro Yamamura, Sharanjot Saini, Guoren Deng, Z. Laura Tabatabai, Shahana Majid, Rajvir Dahiya

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Prostate cancer incidence and mortality rates are higher in African-American (AA) than in European-American (EA) men. The main objective of this study was to elucidate the role of miR-130b as a contributor to prostate cancer health disparity in AA patients. We also determined whether miR-130b is a prognostic biomarker and a new therapeutic candidate for AA prostate cancer. A comprehensive approach of using cell lines, tissue samples, and the TCGA database was employed. We performed a series of functional assays such as cell proliferation, migration, invasion, RT2-PCR array, qRT-PCR, cell cycle, luciferase reporter, immunoblot, and IHC. Various statistical approaches such as Kaplan–Meier, uni-, and multivariate analyses were utilized to determine the clinical significance of miR-130b. Our results showed that elevated levels of miR-130b correlated with race disparity and PSA levels/failure and acted as an independent prognostic biomarker for AA patients. Two tumor suppressor genes, CDKN1B and FHIT, were validated as direct functional targets of miR-130b. We also found race-specific cell-cycle pathway activation in AA patients with prostate cancer. Functionally, miR-130b inhibition reduced cell proliferation, colony formation, migration/invasion, and induced cell-cycle arrest. Inhibition of miR-130b modulated critical prostate cancer–related biological pathways in AA compared with EA prostate cancer patients. In conclusion, attenuation of miR-130b expression has tumor suppressor effects in AA prostate cancer. miR-130b is a significant contributor to prostate cancer racial disparity as its overexpression is a risk factor for poor prognosis in AA patients with prostate cancer. Thus, regulation of miR-130b may provide a novel therapeutic approach for the management of prostate cancer in AA patients.

Original languageEnglish (US)
Pages (from-to)585-598
Number of pages14
JournalCancer Prevention Research
Volume12
Issue number9
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hashimoto, Y., Shiina, M., Dasgupta, P., Kulkarni, P., Kato, T., Wong, R. K., Tanaka, Y., Shahryari, V., Maekawa, S., Yamamura, S., Saini, S., Deng, G., Laura Tabatabai, Z., Majid, S., & Dahiya, R. (2019). Upregulation of MIR-130b contributes to risk of poor prognosis and racial disparity in African-American Prostate Cancer. Cancer Prevention Research, 12(9), 585-598. https://doi.org/10.1158/1940-6207.CAPR-18-0509