| Experiment ID | EXP00300 |
| Reference | Title: Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities. Author: Wang BD, Ceniccola K, Yang Q, Andrawis R, Patel V, Ji Y, RhimJ, Olender J, Popratiloff A, Latham P, Lai Y, Patierno SR, Lee NH. Journal: Clin Cancer Res. 2015 Nov 1;21(21):4970-84. doi: 10.1158/1078-0432.CCR-14-1566.Epub 2015 Jun 18. Abstract: PURPOSE: African Americans (AA) exhibit higher rates of prostate cancer incidenceand mortality compared with European American (EA) men. In addition tosocioeconomic influences, biologic factors are believed to play a critical rolein prostate cancer disparities. We investigated whether population-specific and-enriched miRNA-mRNA interactions might contribute to prostate cancerdisparities.EXPERIMENTAL DESIGN: Integrative genomics was used, combining miRNA and mRNAprofiling, miRNA target prediction, pathway analysis, and functional validation, to map miRNA-mRNA interactions associated with prostate cancer disparities.RESULTS: We identified 22 AA-specific and 18 EA-specific miRNAs in prostatecancer versus patient-matched normal prostate, and 10 AA-enriched/-depletedmiRNAs in AA prostate cancer versus EA prostate cancer comparisons. Many of thesepopulation-specific/-enriched miRNAs could be paired with target mRNAs thatexhibited an inverse pattern of differential expression. Pathway analysisrevealed EGFR (or ERBB) signaling as a critical pathway significantly regulatedby AA-specific/-enriched mRNAs and miRNA-mRNA pairings. Novel miRNA-mRNA pairingswere validated by qRT-PCR, Western blot, and/or IHC analyses in prostate cancerspecimens. Loss/gain of function assays performed in population-specific prostatecancer cell lines confirmed miR-133a/MCL1, miR-513c/STAT1, miR-96/FOXO3A,miR-145/ITPR2, and miR-34a/PPP2R2A as critical miRNA-mRNA pairings drivingoncogenesis. Manipulating the balance of these pairings resulted in decreasedproliferation and invasion, and enhanced sensitization to docetaxel-inducedcytotoxicity in AA prostate cancer cells.CONCLUSIONS: Our data suggest that AA-specific/-enriched miRNA-mRNA pairings may play a critical role in the activation of oncogenic pathways in AA prostatecancer. Our findings also suggest that miR-133a/MCL1, miR-513c/STAT1, andmiR-96/FOXO3A may have clinical significance in the development of novelstrategies for treating aggressive prostate cancer. PMID: 26089375 |
| Expressiion Profile | Description: MicroRNA expression profiling of the prostate biopsy samples from African American and European American prostate cancer patients Organism: Homo sapiens GEO ID: GSE64318 Platform: GPL8227 Number of samples: 54 |
| Design and Sample | Cancer Type: prostate cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: cancer vs normal Case Sample: prostate cancer Control Sample: normal tissue Num of Case: 27 Num of Control: 27 Quantification Software: Limma Num of miRNAs: 723 |
| Identification | Num of Up: 38 Num of Down: 42 |