Abstract 1778: MALAT1 and TUG1 long non-coding RNAs signalling mechanisms in response to SRPK1 inhibitor in prostate cancer

Abstract Introduction: Prostate cancer (PCa) is a leading cause of cancer death, and there are significant racial disparities in patient outcomes. Non-coding RNAs (lncRNAs) MALAT1 and TUG1 are recognised for their roles in oncogenic pathways. Their precise interacting mechanisms with splicing factors and splicing factor kinases is understudied. Aim: This study aims to map the biological pathways influenced by TUG1, MALAT1 in response to SRPK1 inhibitor prostate cancer cells Materials and Methods: Bioinformatics tools LncSEA 2.0, STRING, DAVID and Reactome were used to analyse the interactions between MALAT1, TUG1 and relevant miRNAs and their target genes. Resozuring cell viability assay was used to measure PCa cell viability (PC-3 cells vs HEK) in response to Sphinx31 at 24hrs and 48hrs. Next, RT-qPCR was used to measure gene expression levels of the lncRNAs. Results and Discussion: MALAT1 and TUG1 act as competing endogenous RNAs (ceRNAs) to sponge miRNAs that regulate critical tumour proliferation and migration genes, including PTEN and BCL2. SRPK1 regulates splicing factors to enhance tumour aggressiveness. The MALAT1-miR-125b-BCL2 and TUG1-miR-29b-PTEN axes are critical pathways for PCa progression, especially in advanced stages. Sphinx31 is cytotoxic in a time dependent manner to the PCa cells, while the 2 lncRNAs expression is elevated in PCa cells prior to Sphinx31 treatment. Conclusion: Targeting lncRNA-miRNA networks and splicing factor interactions, especially MALAT1 and SRPK1, is a potential therapeutic target for PCa. Citation Format: Linomtha Gabada, Zodwa Dlamini, Rahaba Makgotso Marima. MALAT1 and TUG1 long non-coding RNAs signalling mechanisms in response to SRPK1 inhibitor in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1778.