Abstract PO-128: Interrogating the role of race-related alternative splicing of SEMA3C in prostate cancer

Abstract

Abstract The age-adjusted incidence and mortality rates for prostate cancer (PCa) among African American (AA) men are 1.6- and 2.4-fold greater, respectively, than among white men. These disparities likely result from a complex interplay among social, psycho-social, lifestyle, environmental, health system, and biological determinants of health. Despite the contribution of biological determinants of health, very few studies have utilized this population-based difference to identify the molecular mechanisms underlying race-related tumor aggressiveness. We have previously identified Semaphorin 3C (SEMA3C) as a novel alternatively spliced gene in PCa between AA and white patients. SEMA3C has been shown to be associated with increased cancer growth, poor prognosis in lung, breast, gastric, and ovarian cancers, and promotion of cell migration and invasion in PCa. To further study the significance of race-related skipping/inclusion of SEMA3C exon 19 in PCa cell biology, we used CRISPR/Cas9 technology to engineer a PCa cell line (DU145) expressing the SEMA3C variant skipping exon 19. Proliferation assays were performed with the established cell lines, and the SEMA3C exon 19 KO populations exhibited decreased proliferation rates, compared with the wild-type DU145 cells that express the SEMA3C variant including exon 19. These data suggest race-related alternative splicing of SEMA3C may have an impact on PCa aggressiveness in patients. Current and future experiments focus on interrogating the effect of race-related SEMA3C alternative splicing on PCa cell migration and invasion as well as in vivo tumor formation and metastasis. These findings will provide an increased understanding of the role of race-related alternative splicing in PCa disparities and potentially a new target for development of precision medicine interventions. Citation Format: Tyler A. Allen, Jay Chandar, Bonnie L. Lacroix, Steven R. Patierno, Daniel J. George, Jennifer A. Freedman. Interrogating the role of race-related alternative splicing of SEMA3C in prostate cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-128.