Abstract B069: Upregulation of miR-130b contributes to risk of poor prognosis and racial disparity in African-American prostate cancer

Abstract

Abstract Prostate cancer (PC) 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 PC health disparity in AA patients. We also determined whether miR-130b is a prognostic biomarker and a new therapeutic candidate for AA PC. 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 immunohistochemistry. 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 PC patients. Functionally, miR-130b inhibition reduced cell proliferation, colony formation, migration/invasion and induced cell cycle arrest. Inhibition of miR-130b modulated critical PC related biological pathways in AA compared to EA PC patients. In conclusion, attenuation of miR-130b expression has tumor suppressor effects in AA PC. miR-130b is a significant contributor to PC racial disparity as its overexpression is a risk factor for poor prognosis in AA PC patients. Thus, regulation of miR-130b may provide a novel therapeutic approach for the management of PC in AA patients. Citation Format: Yutaka Hashimoto, Marisa Shiina, Yuichiro Tanaka, Rajvir Dahiya, Shahana Majid. Upregulation of miR-130b contributes to risk of poor prognosis and racial disparity in African-American prostate cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B069.