biostudies-literatureUnknown32(4)Montero-Hidalgo AJProstate cancer (PCa) is the second most common cancer among men worldwide. The main screening tool remains the prostate-specific antigen (PSA), which shows significant limitations, including poor sensitivity/specificity. Therefore, establishing accurate non-invasive diagnostic biomarkers remains an unmet clinical need in PCa. In this context, the splicing process dysregulation represents a PCa hallmark. Here, plasma SRRM1, SNRNP200, and SRSF3 levels, previously identified to play a pathophysiological role in PCa, were determined in control individuals (<i>n</i> = 40) and PCa patients (<i>n</i> = 166). We found that plasma SRRM1 and SNRNP200 levels were elevated in PCa patients and discriminated between control individuals and PCa patients. High plasma SRRM1 levels were associated with a shorter castration-resistant PCa-free survival and correlated with androgen-receptor (AR)/AR-splicing variant 7 (AR-V7) expression levels and activity in PCa tissues. Therefore, the functional and molecular effects of <i>in vivo</i> SRRM1 silencing were then tested in 22Rv1-derived xenograft tumors. <i>In vivo</i> SRRM1 silencing reduced aggressiveness features and altered AR/AR-V7 activity. Our data reveal that SRRM1 holds potential as a non-invasive diagnostic and prognostic biomarker and novel therapeutic target in PCa, offering a clinically relevant opportunity worth exploring in humans.Molecular therapy. Oncology200910https://www.ebi.ac.uk/biostudies/studies/S-EPMC11697196biostudies-literatureClinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target.PMC11697196Rangel-Zuniga OAPorcel-Pastrana FLuque RMSarmento-Cabral AJimenez-Vacas JMPerez-Gomez JMMontero-Hidalgo AJGonzalez-Serrano TOrtega-Bellido MChamorro-Castillo LGahete MDGomez-Gomez ECampos-Hernandez JPCarrasco-Valiente JGalan-Canete MSanchez-Sanchez RfalseClinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target.Prostate cancer (PCa) is the second most common cancer among men worldwide. The main screening tool remains the prostate-specific antigen (PSA), which shows significant limitations, including poor sensitivity/specificity. Therefore, establishing accurate non-invasive diagnostic biomarkers remains an unmet clinical need in PCa. In this context, the splicing process dysregulation represents a PCa hallmark. Here, plasma SRRM1, SNRNP200, and SRSF3 levels, previously identified to play a pathophysiological role in PCa, were determined in control individuals (<i>n</i> = 40) and PCa patients (<i>n</i> = 166). We found that plasma SRRM1 and SNRNP200 levels were elevated in PCa patients and discriminated between control individuals and PCa patients. High plasma SRRM1 levels were associated with a shorter castration-resistant PCa-free survival and correlated with androgen-receptor (AR)/AR-splicing variant 7 (AR-V7) expression levels and activity in PCa tissues. Therefore, the functional and molecular effects of <i>in vivo</i> SRRM1 silencing were then tested in 22Rv1-derived xenograft tumors. <i>In vivo</i> SRRM1 silencing reduced aggressiveness features and altered AR/AR-V7 activity. Our data reveal that SRRM1 holds potential as a non-invasive diagnostic and prognostic biomarker and novel therapeutic target in PCa, offering a clinically relevant opportunity worth exploring in humans.2024-01-01T00:00:00Z2024 Dec2026-06-02T08:00:53.586Z2026-04-16T03:10:18.492ZS-EPMC116971963975825010.1016/j.omton.2024.200910