Abstract PR-17: The role of HMGA2 and CLK3 in prostate cancer health disparities

Abstract

Abstract African American men (AA) suffer disproportionately from prostate cancer (PCa) displaying higher incidence and mortality rates when compared to Caucasian-American men (CA). Recent studies have shown that high mobility group A2 (HMGA2), a non-histone chromatin binding protein, plays a critical role in promoting metastasis. HMGA2 full-length/wild-type and truncated (lacking the 3'UTR) isoforms are overexpressed in several cancers, however, their distinct roles in PCa have not been reported. Literature has previously revealed a splicing factor, CDC-like kinase 3 (CLK3), that promotes splicing of wild-type HMGA2 to create the truncated HMGA2 isoform. We hypothesize that HMGA2 isoforms may play differential roles to promote PCa progression according to ethnicity. qPCR analysis of patient tissue of varying PCa stages was conducted to look at the mRNA expression of HMGA2 isoforms and CLK3. RNA-Seq was performed on LNCaP prostate cancer cell lines stably overexpressing wild-type or truncated HMGA2 and compared to Neo control. Both wild-type and truncated HMGA2 increased with increased PCa gleason grade. AA when compared to CA, displayed higher levels of truncated HMGA2 and its splicing factor, CLK3. RNA-Seq analysis revealed distinct gene sets regulated by truncated HMGA2 compared to wild-type HMGA2, including upregulation of a distinct set of genes involved in androgen signaling. These results indicate that HMGA2 isoforms are disproportionately expressed in AA and CA and increase with PCa progression. The regulation of differential genes by HMGA2 isoforms suggest that they may use distinct pathways to promote PCa. Citation Format: Taaliah Campbell, Ohuod Hawsawi, Valerie Odero-Marah. The role of HMGA2 and CLK3 in prostate cancer health disparities [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR-17.