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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
|
| Series: | Molecular Therapy: Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924001528 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846124824197332992 |
|---|---|
| author | Antonio J. Montero-Hidalgo Enrique Gómez-Gómez Manuel Galán-Cañete Francisco Porcel-Pastrana Jesús M. Pérez-Gómez María Ortega-Bellido Julia Carrasco-Valiente Laura Chamorro-Castillo Juan P. Campos-Hernández Oriol A. Rangel-Zuñiga Teresa González-Serrano Rafael Sánchez-Sánchez André Sarmento-Cabral Manuel D. Gahete Juan M. Jiménez-Vacas Raúl M. Luque |
| author_facet | Antonio J. Montero-Hidalgo Enrique Gómez-Gómez Manuel Galán-Cañete Francisco Porcel-Pastrana Jesús M. Pérez-Gómez María Ortega-Bellido Julia Carrasco-Valiente Laura Chamorro-Castillo Juan P. Campos-Hernández Oriol A. Rangel-Zuñiga Teresa González-Serrano Rafael Sánchez-Sánchez André Sarmento-Cabral Manuel D. Gahete Juan M. Jiménez-Vacas Raúl M. Luque |
| author_sort | Antonio J. Montero-Hidalgo |
| collection | DOAJ |
| description | 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 (n = 40) and PCa patients (n = 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 in vivo SRRM1 silencing were then tested in 22Rv1-derived xenograft tumors. In vivo 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. |
| format | Article |
| id | doaj-art-b52521c47f034f6387d9278eeb7e2d1f |
| institution | Kabale University |
| issn | 2950-3299 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-b52521c47f034f6387d9278eeb7e2d1f2024-12-13T11:09:50ZengElsevierMolecular Therapy: Oncology2950-32992024-12-01324200910Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic targetAntonio J. Montero-Hidalgo0Enrique Gómez-Gómez1Manuel Galán-Cañete2Francisco Porcel-Pastrana3Jesús M. Pérez-Gómez4María Ortega-Bellido5Julia Carrasco-Valiente6Laura Chamorro-Castillo7Juan P. Campos-Hernández8Oriol A. Rangel-Zuñiga9Teresa González-Serrano10Rafael Sánchez-Sánchez11André Sarmento-Cabral12Manuel D. Gahete13Juan M. Jiménez-Vacas14Raúl M. Luque15Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Urology Service, HURS/IMIBIC, 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Urology Service, HURS/IMIBIC, 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Urology Service, HURS/IMIBIC, 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Urology Service, HURS/IMIBIC, 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Internal Medicine Unit, HURS/IMIBIC, 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Anatomical Pathology Service, HURS, 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Anatomical Pathology Service, HURS, 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Cordoba, SpainMaimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Cordoba, Spain; Corresponding author: Juan M. Jiménez-Vacas, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain.Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14004 Cordoba, Spain; Hospital Universitario Reina Sofía (HURS), 14004 Cordoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Cordoba, Spain; Corresponding author: Raúl M. Luque, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain.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 (n = 40) and PCa patients (n = 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 in vivo SRRM1 silencing were then tested in 22Rv1-derived xenograft tumors. In vivo 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.http://www.sciencedirect.com/science/article/pii/S2950329924001528MT: Novel therapeutic targets and biomarker development Special IssueSRRM1SNRNP200SRSF3prostate cancerbiomarker |
| spellingShingle | Antonio J. Montero-Hidalgo Enrique Gómez-Gómez Manuel Galán-Cañete Francisco Porcel-Pastrana Jesús M. Pérez-Gómez María Ortega-Bellido Julia Carrasco-Valiente Laura Chamorro-Castillo Juan P. Campos-Hernández Oriol A. Rangel-Zuñiga Teresa González-Serrano Rafael Sánchez-Sánchez André Sarmento-Cabral Manuel D. Gahete Juan M. Jiménez-Vacas Raúl M. Luque Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target Molecular Therapy: Oncology MT: Novel therapeutic targets and biomarker development Special Issue SRRM1 SNRNP200 SRSF3 prostate cancer biomarker |
| title | Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target |
| title_full | Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target |
| title_fullStr | Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target |
| title_full_unstemmed | Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target |
| title_short | Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target |
| title_sort | clinical value of circulating splicing factors in prostate cancer srrm1 as a novel predictive biomarker and therapeutic target |
| topic | MT: Novel therapeutic targets and biomarker development Special Issue SRRM1 SNRNP200 SRSF3 prostate cancer biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924001528 |
| work_keys_str_mv | AT antoniojmonterohidalgo clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT enriquegomezgomez clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT manuelgalancanete clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT franciscoporcelpastrana clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT jesusmperezgomez clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT mariaortegabellido clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT juliacarrascovaliente clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT laurachamorrocastillo clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT juanpcamposhernandez clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT oriolarangelzuniga clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT teresagonzalezserrano clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT rafaelsanchezsanchez clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT andresarmentocabral clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT manueldgahete clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT juanmjimenezvacas clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget AT raulmluque clinicalvalueofcirculatingsplicingfactorsinprostatecancersrrm1asanovelpredictivebiomarkerandtherapeutictarget |