Clinical 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.
Authors
- Enrique Gómez‐Gómez (ORCID: https://orcid.org/0000-0002-8753-3306)
- Raul Miguel Luque (ORCID: https://orcid.org/0000-0002-7585-1913)
- Oriol Alberto Rangel-Zúñiga (ORCID: https://orcid.org/0000-0003-3495-5705)
- J.P. Campos-Hernández (ORCID: https://orcid.org/0000-0002-9994-5754)
- Manuel David Gahete (ORCID: https://orcid.org/0000-0002-4578-2179)
- Teresa González Serrano (ORCID: https://orcid.org/0000-0002-8034-0480)
- Francisco Porcel-Pastrana (ORCID: https://orcid.org/0000-0002-1664-2556)
- Juan M. Jiménez‐Vacas (ORCID: https://orcid.org/0000-0003-4391-3726)
- Julia Carrasco‐Valiente
- M. Bellido (ORCID: https://orcid.org/0000-0003-0845-2610)
- Antonio J. Montero‐Hidalgo (ORCID: https://orcid.org/0000-0002-1948-7512)
- André Sarmento-Cabral
- Jesús M. Pérez‐Gómez (ORCID: https://orcid.org/0000-0003-1785-9797)
- Rafael Sánchez-Sánchez (ORCID: https://orcid.org/0000-0002-9497-2315)
- Manuel Galán-Cañete
- Laura Chamorro-Castillo
Institutions
- Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (ES)
- Instituto Maimónides de Investigación Biomédica de Córdoba (ES)
- Centro de Investigación Biomédica en Red (ES)
- Hospital Universitario Reina Sofía (ES)
- University of Córdoba (ES)
Publication Details
- Journal
- Molecular Therapy Oncology
- Published
- 2024-11-23
- DOI
- https://doi.org/10.1016/j.omton.2024.200910
- Citations
- 1
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 0.23
Funders
- Ministerio de Ciencia, Innovación y Universidades
- European Commission
- Ministerio de Sanidad, Servicios Sociales e Igualdad
- Junta de Andalucía
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
- Instituto de Salud Carlos III
- European Regional Development Fund
- European Social Fund