Abstract 1554: LIM Domain 7 (LMO7) splice variant influences prostate cancer biology

Abstract

Abstract LIM Domain 7 (LMO7) has been shown to participate in cell-cell junction formation through interaction with afadin and α-actinin. It has also been reported to collaborate with Rho kinase to regulate actin filament formation and to activate the Rho-myocardin-related transcription factor serum response factor pathway. Additionally, LMO7 itself may function as a transcription factor, regulating the expression of genes involved in Epithelial Mesenchymal Transition (EMT). Alternative splicing of LMO7 has the potential to modulate its function. Previously, we reported LMO7 as a target that is alternatively spliced in prostate cancer (PCa) between self-reported Black and White patients. In addition, by analyzing expression of LMO7 splice variants in The Cancer Genome Atlas (TCGA) data, we previously reported increased expression of a LMO7 splice variant skipping exon 12 in breast, lung and liver cancer compared with paired normal tissues. In the present study, we found that LMO7 is downregulated in metastatic PCa specimens within the Stand Up To Cancer cohort. To investigate the functional impact of expression of the LMO7 splice variant skipping exon 12 in PCa, we utilized CRISPR-Cas9 methodology to delete LMO7 exon 12 in PCa cells and assessed resulting alterations in PCa cell biology. The LMO7 exon 12 deleted PC3 PCa cells exhibited enhanced migratory potential compared with parental PCa cells. An Immunofluorescence (IF) assay showed weak staining of cell-cell junctions in LMO7 exon 12 deleted PCa cells compared with parental PCa cells. Moreover, IF staining showed retardation in f-actin in LMO7 exon 12 deleted PCa cells compared with parental PCa cells. As E-Cadherin is often inhibited during EMT, we assessed the level of E-Cadherin by western blot and real-time polymerase chain reaction (PCR). These analyses revealed that E-Cadherin protein as well as messenger RNA is suppressed in LMO7 exon 12 deleted PCa cells compared with parental PCa cells. These findings suggest a role for skipping of LMO7 exon 12 in disrupting PCa cell-cell junctions, down-regulating E-Cadherin in PCa and enhancing PCa cell migratory potential, consistent with EMT. Citation Format: Muthana Al Abo, Daniel J. George, Zefeng Wang, Steven R. Patierno, Jennifer A. Freedman, Alice Jiang. LIM Domain 7 (LMO7) splice variant influences prostate cancer biology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1554.