Gabada, LinomthaBasera, AfraAlabi, Babatunde AdebolaDlamini, ZodwaMojakgomo, Rahaba Makgotso2025-11-252026Gabada, L., Basera, A., Alabi, B.A. et al. Targeting SRPK1 to regulate alternative splicing in prostate cancer: the roles of MALAT1 and TUG1. Molecular Biology Reports 53, 55 (2026). https://doi.org/10.1007/s11033-025-11185-9.0301-4851 (print)1573-4978 (online)10.1007/s11033-025-11185-9http://hdl.handle.net/2263/105476DATA AVAILABILITY : Data is provided within the manuscript.BACKGROUND : Prostate cancer (PCa) is a leading cause of cancer-related mortality, with significant racial disparities in outcomes. Long non-coding RNAs (lncRNAs) MALAT1 and TUG1 are implicated in oncogenic pathways. Aberrant RNA splicing, a hallmark of cancer, is often driven by dysregulation of serine-arginine protein kinase 1 (SRPK1), a key spliceosome regulator. The relationship between lncRNAs of splicing factors in cancer pathways remains underexplored, and thus, this study aimed to elucidate the roles of MALAT1 and TUG1 lncRNAs in relation to the SRPK1 inhibitor SPHINX31 in PCa. METHODS : Bioinformatics tools were used to analyze interactions between` MALAT1, TUG1, relevant miRNAs, and target genes. A resazurin assay assessed PCa cell viability (PC-3 vs. HEK293) in response to SPHINX31 at 24 and 48 h. RT-qPCR was used to quantify MALAT1 and TUG1 lncRNAs expression levels. RESULTS : The Alamar Blue assay indicated a time-dependent reduction in PC3 cell viability with 3 µM SPHINX31, particularly at 48 h. RT-qPCR revealed significant regulation of MALAT1 and TUG1, highlighting SRPK1’s role in RNA pathways critical for tumor survival. SPHINX31 induced similar cytotoxic effects in HEK293 cells, illustrating the need for selective tumor specificity. MALAT1 expression was upregulated at 24 h, followed by a decline at 48 h, indicating cumulative cellular stress in PC-3 cells. DISCUSSION : This study demonstrated that SRPK1 inhibition alters lncRNA expression and splicing-related events in PCa. These findings highlight SPHINX31’s potential as a therapeutic agent, especially in combination with treatments like Olaparib, necessitating further optimization for selectivity and reduced off-target effects.en© The Author(s), under exclusive licence to Springer Nature B.V. 2025 The original publication is available at : http://link.springer.com/journal/11033.Prostate cancer (PCa)MALAT1TUG1Long non-coding RNAs (lncRNAs)Serine-arginine protein kinase 1 (SRPK1)CeRNAsAngiogenesisAlternative splicingPostprint Article