Validation and Interrogation of Differentially Expressed and Alternately Spliced Genes in African American Prostate Cancer
Abstract
We have discovered RNA splicing as a novel mechanism underlying tumor aggressiveness and drug resistance in prostate cancer (PCa) in African American (AA) patients. To interrogate further the contribution of RNA splicing to PCa disparities, we have collected blood and tissue specimens of varying Gleason grade from AA and white patients for study. In addition, we have identified single nucleotide polymorphisms (SNPs) predicted to regulate RNA splicing in race-related alternatively spliced genes involved in stemness that associate with race-related PCa risk or PCa survival and genome-wide SNPs predicted to regulate RNA splicing that associate with advanced PCa. Furthermore, we have developed a splice-switching oligonucleotide (SSO) that specifically inhibits expression of the pathogenic androgen receptor (AR)-variant 7 (V7), while maintaining expression of full-length AR, which has therapeutic value. This SSO inhibits proliferation of PCa cells and restores sensitivity to an AR inhibitor. It can be delivered directly to PCa cells without transfection reagent. Ultimately, this study will elucidate further molecular mechanisms underlying PCa in AA men and aid in development of new approaches for prevention and treatment that will mitigate PCa disparities for AAs and improve outcomes for men of all races with aggressive disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1098424
Entities
People
- Jennifer Freedman
- Steven R. Patierno
Organizations
- Duke University