Dataset Information

Upregulation of miR-130b Contributes to Risk of Poor Prognosis and Racial Disparity in African-American Prostate Cancer.

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.

SUBMITTER: Hashimoto Y

PROVIDER: S-EPMC7327781 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Upregulation of miR-130b Contributes to Risk of Poor Prognosis and Racial Disparity in African-American Prostate Cancer.

Hashimoto Yutaka Y Shiina Marisa M Dasgupta Pritha P Kulkarni Priyanka P Kato Taku T Wong Ryan K RK Tanaka Yuichiro Y Shahryari Varahram V Maekawa Shigekatsu S Yamamura Soichiro S Saini Sharanjot S Deng Guoren G Tabatabai Z Laura ZL Majid Shahana S Dahiya Rajvir R

Cancer prevention research (Philadelphia, Pa.) 20190702 9

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 f ...[more]

PMID: 31266828

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Project description:BackgroundAfrican Americans (AAs) in the United States are known to have a higher incidence and mortality for Prostate Cancer (PCa). The drivers of this epidemiological disparity are multifactorial, including socioeconomic factors leading to lifestyle and dietary issues, healthcare access problems, and potentially tumor biology.Recent findingsAlthough recent evidence suggests once access is equal, AA men have equal outcomes to Caucasian American (CA) men, differences in PCa incidence remain, and there is much to do to reverse disparities in mortality across the USA. A deeper understanding of these issues, both at the clinical and molecular level, can facilitate improved outcomes in the AA population. This review first discusses PCa oncogenesis in the context of its diverse hallmarks before benchmarking key molecular and genomic differences for PCa in AA men that have emerged in the recent literature. Studies have emphasized the importance of tumor microenvironment that contributes to both the unequal cancer burden and differences in clinical outcome between the races. Management of comorbidities like obesity, hypertension, and diabetes will provide an essential means of reducing prostate cancer incidence in AA men. Although requiring further AA specific research, several new treatment strategies such as immune checkpoint inhibitors used in combination PARP inhibitors and other emerging vaccines, including Sipuleucel-T, have demonstrated some proven efficacy.ConclusionGenomic profiling to integrate clinical and genomic data for diagnosis, prognosis, and treatment will allow physicians to plan a "Precision Medicine" approach to AA men. There is a pressing need for further research for risk stratification, which may allow early identification of AA men with higher risk disease based on their unique clinical, genomic, and immunological profiles, which can then be mapped to appropriate clinical trials. Treatment options are outlined, with a concise description of recent work in AA specific populations, detailing several targeted therapies, including immunotherapy. Also, a summary of current clinical trials involving AA men is presented, and it is important that policies are adopted to ensure that AA men are actively recruited. Although it is encouraging that many of these explore the lifestyle and educational initiatives and therapeutic interventions, there is much still work to be done to reduce incidence and mortality in AA men and equalize current racial disparities.

Dataset Information

Upregulation of miR-130b Contributes to Risk of Poor Prognosis and Racial Disparity in African-American Prostate Cancer.

Publications

Upregulation of miR-130b Contributes to Risk of Poor Prognosis and Racial Disparity in African-American Prostate Cancer.

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