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The role of miR-24 as a race related genetic factor in prostate cancer
- Source :
- Oncotarget, vol 8, iss 10, Oncotarget
- Publication Year :
- 2017
- Publisher :
- eScholarship, University of California, 2017.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Urologic Diseases
Male
Pathology
medicine.medical_specialty
Aging
Oncology and Carcinogenesis
Down-Regulation
Apoptosis
medicine.disease_cause
ETV1
Cell Line
03 medical and health sciences
Prostate cancer
pathway modulation
0302 clinical medicine
Cell Line, Tumor
microRNA
parasitic diseases
Genetics
Medicine
2.1 Biological and endogenous factors
Humans
Aetiology
Cancer
Cell Proliferation
miRNA
race related prostate cancer
Tumor
DNA methylation
business.industry
Prostate Cancer
Incidence
Prostatic Neoplasms
Transfection
medicine.disease
3. Good health
MicroRNAs
030104 developmental biology
Real-time polymerase chain reaction
Oncology
030220 oncology & carcinogenesis
Cancer research
Ectopic expression
business
Carcinogenesis
Research Paper
Biotechnology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Oncotarget, vol 8, iss 10, Oncotarget
- Accession number :
- edsair.doi.dedup.....8188f5cf5735ef43c4e5352657852418