Abstract A034: SRPK1-mediated distinct transcriptomic reprogramming in cervical cancer: Insights into splicing regulation in the African context

Abstract Background: Cervical cancer remains a significant public health burden in Sub-Saharan Africa, where high-risk human papillomavirus (HPV) infections are prevalent and health system inequities contribute to poor outcomes. Beyond viral oncogenes, HPV modulates host gene expression through alternative splicing, a process increasingly recognized as a driver of cancer progression. The serine/arginine-rich protein kinase 1 (SRPK1) regulates splicing via phosphorylation of SRSF1 and is emerging as a potential therapeutic target. However, the transcriptomic consequences of SRPK1 inhibition in HPV-associated cervical cancer, particularly in the African context, remain underexplored. Methods: This study investigates how SRPK1 inhibition alters splicing and gene expression in cervical cancer models relevant to the African disease landscape. SiHa (HPV16-positive) and C33A (HPV-negative) cell lines were treated with the SRPK1 inhibitor SPHINX31. Cellular phenotypes were assessed via resazurin viability assays, flow cytometric cell cycle analysis, and Annexin V/PI apoptosis assays. RNA sequencing was performed to evaluate global transcriptomic changes, including differential expression and alternative splicing events. Results and Discussion: SRPK1 inhibition did not significantly affect cell viability or apoptosis in either cell line. However, RNA-seq revealed distinct transcriptomic reprogramming between HPV-positive and HPV-negative models. In HPV-positive SiHa cells, proliferation-related genes were downregulated, accompanied by upregulation of metabolic and xenobiotic response pathways, indicating a unique adaptive response linked to viral oncogene presence. Conversely, HPV-negative C33A cells showed a broader downregulation of transcriptional regulators and increased expression of metabolic genes, reflecting alternative oncogenic pathways independent of HPV infection. Notably, splicing alterations also differed: SiHa cells exhibited splicing changes enriched in focal adhesion and endoplasmic reticulum targeting genes, while C33A cells showed splicing events associated with mitochondrial organization and transcriptional regulation. Conclusion: These findings suggest that SRPK1 inhibition influences RNA splicing and gene expression without altering immediate cellular phenotypes. Importantly, the identification of HPV-specific splicing signatures in models relevant to African cervical cancer supports SRPK1 as a potential modulator of RNA processing with therapeutic relevance. This study contributes to the molecular understanding of cervical cancer disparities and highlights the need for splicing-targeted approaches in precision oncology across underserved populations. Citation Format: Zodwa Dlamini, Afra T. Basera, David O. Bates, Rahaba Marima, Mohammed Alaouna, Janie Duvenhage. SRPK1-mediated distinct transcriptomic reprogramming in cervical cancer: Insights into splicing regulation in the African context [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A034.