The role of miR-24 as a race related genetic factor in prostate cancer
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Yutaka Hashimoto1,*, Marisa Shiina1,*, Taku Kato1, Soichiro Yamamura1, Yuichiro Tanaka1, Shahana Majid1, Sharanjot Saini1, Varahram Shahryari1, Priyanka Kulkarni1, Pritha Dasgupta1, Yozo Mitsui1, Mitsuho Sumida1, Guoren Deng1, Laura Tabatabai2, Deepak Kumar3, Rajvir Dahiya1
1Department of Urology, VA Medical Center and UCSF, San Francisco, CA 94121, USA
2Department of Pathology, Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, CA 94121, USA
3Julius L. Chambers Biomedical/Biotechnology Research Institute (BBRI), Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC 27707, USA
*These authors contributed equally to this work
Rajvir Dahiya, email: Rdahiya@ucsf.edu
Keywords: race related prostate cancer, miRNA, pathway modulation, DNA methylation
Received: December 01, 2016 Accepted: January 24, 2017 Published: February 02, 2017
The incidence of prostate cancer (PCa) among African-Americans (AfA) is significantly higher than Caucasian-Americans (CaA) but the genetic basis for this disparity is not known. To address this problem, we analyzed miRNA expression in AfA (n = 81) and CaA (n = 51) PCa patients. Here, we found that miR-24 is differentially expressed in AfA and CaA PCa patients and attempt to clarify its role in AfA patients. Also, the public sequencing data of the miR-24 promoter confirmed that it was highly methylated and down-regulated in PCa patients. Utilizing a VAMCSF and NDRI patient cohorts, we discovered that miR-24 expression was linked to a racial difference between AfA/CaA PCa patients. Interestingly, miR-24 was restored after treatment of PCa cells with 5Aza-CdR in an AfA cell line (MDA-PCa-2b), while restoration of miR-24 was not observed in CaA cells, DU-145. Ectopic expression of miR-24 showed decreased growth and induced apoptosis, though the effect was less in the CaA cell line compared to the AfA cell line. Finally, we found unique changes in biological pathways and processes associated with miR-24 transfected AfA cells by quantitative PCR-based gene expression array. Evaluation of the altered pathways showed that AR, IGF1, IGFBP5 and ETV1 were markedly decreased in the AfA derived cell line compared with CaA cells, and there was a reciprocal regulatory relationship of miR-24/target expression in prostate cancer patients. These results demonstrate that miR-24 may be a central regulator of key events that contribute to race-related tumorigenesis and has potential to be a therapeutic agent for PCa treatment.
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