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Introduction: African Americans (AA) exhibit higher prostate cancer (PCa) incidence and mortality rates compared to European American (EA) men. In addition to socioeconomic influences affecting access to health care, biological risk factors may also play a critical role in PCa disparities.
Methods: To identify the biological elements involved in the differential biological properties between AA and EA PCa, we applied integrative genomics analysis by combining miRNA and mRNA profiling, miRNA target prediction, pathway analysis and functional validation, to map miRNA-mRNA interactions associated with PCa disparities. In this study, we have first identified 22 AA-specific and 18 EA-specific miRNAs in PCa versus patient-matched normal prostate, and 10 ‘AA-enriched/-depleted’ miRNAs in AA PCa versus EA PCa comparisons.
Results: Further pathway analyses have revealed that many population-specific and -enriched miRNAs-mRNA pairings were over-represented in several oncogenic pathways, including the PI3K/AKT and EGF signaling pathways. Novel miRNA-mRNA pairings were validated by qRT-PCR, western blot and/or IHC analyses in PCa specimens. In-vitro functional evaluations were performed in AA-and EA-specific PCa cell lines and confirmed that miR-133a/MCL, miR-513c/STAT1, miR-96/FOXO3A, miR-145/ITPR2 and miR-34a/PPP2R2A as critical miRNA-mRNA pairings contributing to the PCa disparities.
Conclusion: our data suggest that miRNA-mRNA interactions may play a critical role in the activation of oncogenic pathways in AA PCa, and the AA-enriched/-specific miRNA pairings (such as miR-133a/MCL1, miR-513c/STAT1 and miR-96/FOXO3A) may serve as potential PCa biomarkers and novel therapeutic targets in the treatment of aggressive PCa.