PRPF40A is the mammalian ortholog of the yeast protein Prp40, which is an essential splicing factor that participates in the first steps of the spliceosome complex assembly. PRPF40A has been involved in the pathogenesis of neurological disorders, but more importantly in cancer. It has been suggested that PRPF40A could be a possible target of p53 as its expression increases when p53 is mutated (1). PRPF40A is also upregulated in non-small cell lung cancer, showing a surprising association with the expression of hypoxia markers (2). Transcriptomic studies of alternative splicing show that PRPF40A is one of the main upregulated genes in pancreatic ductal adenocarcinoma tissue and that its high expression levels are detrimental for survival. Recent studies suggest that PRPF40A could be used as a biomarker for diagnosis and prognosis of pancreatic cancer (3). Moreover, PRPF40A is altered in 9,17% out of 109 pancreatic cancer events (4) and shows a positive regulation of 9,7 out of 176 RNA TCGA samples (5). According to this data, PRPF40A could be acting as an oncogene in pancreatic cancer. To gain insight into the functional role of PRPF40A in pancreatic cancer, siRNA was used to silence the endogenous expression of PRPF40A in a pancreatic control cell line (HuPANEPI) and three pancreatic cancer cell lines (MiaPaCa, PANC-1 and BxPC-3). Proliferation studies showed that silencing of PRPF40A at 72 h post-transfection results in a decrease of the proliferation rate of the three pancreatic cancer cells in comparison to the control. It was also observed that silencing of the protein results in an increased proportion of apoptotic cells, which was specifically remarkable in MiaPaCa and PANC-1 cell lines. Here, we will show data that support the role of PRPF40A in pancreatic cancer. Our initial hypothesis is that overexpression of PRPF40A can lead to pancreatic cancer, thus decreasing its expression levels could compromise the survival of pancreatic cancer cells. References 1. Becerra S, Andrés¿León E, Prieto¿Sánchez S, Hernández¿Munain C, Suñé C. Prp40 and early events in splice site definition. WIREs RNA. 2016;7(1):17-32. 2. Oleksiewicz U, Liloglou T, Tasopoulou KM, Daskoulidou N, Gosney JR, Field JK, et al. COL1A1, PRPF40A, and UCP2 correlate with hypoxia markers in non-small cell lung cancer. J Cancer Res Clin Oncol. 2017;143(7):1133-41. 3. Huo Z, Zhai S, Weng Y, Qian H, Tang X, Shi Y, et al. PRPF40A as a potential diagnostic and prognostic marker is upregulated in pancreatic cancer tissues and cell lines: an integrated bioinformatics data analysis. OncoTargets Ther. 2019;12:5037-51. 4. Witkiewicz AK, McMillan EA, Balaji U, Baek G, Lin WC, Mansour J, et al. Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat Commun. 2015;6:6744. 5. The Cancer Genome Atlas Program - NCI [Internet]. [citado 5 de mayo de 2022]. Disponible en:https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga.