Spliceosome component SF3B1 as novel prognostic biomarker and therapeutic target for prostate cancer.

Autor:	Jiménez-Vacas JM; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Córdoba, Spain., Herrero-Aguayo V; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Córdoba, Spain., Gómez-Gómez E; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Urology Service, HURS/IMIBIC, Córdoba, Spain., León-González AJ; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Córdoba, Spain., Sáez-Martínez P; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Córdoba, Spain., Alors-Pérez E; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Córdoba, Spain., Fuentes-Fayos AC; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Córdoba, Spain., Martínez-López A; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Anatomical Pathology Service, HURS, Córdoba, Spain., Sánchez-Sánchez R; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Anatomical Pathology Service, HURS, Córdoba, Spain., González-Serrano T; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Anatomical Pathology Service, HURS, Córdoba, Spain., López-Ruiz DJ; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Radiology Service, HURS/IMIBIC., Requena-Tapia MJ; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Urology Service, HURS/IMIBIC, Córdoba, Spain., Castaño JP; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Córdoba, Spain., Gahete MD; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Córdoba, Spain., Luque RM; Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofía (HURS), Córdoba, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Córdoba, Spain. Electronic address: bc2luhur@uco.es.
Jazyk:	angličtina
Zdroj:	Translational research : the journal of laboratory and clinical medicine [Transl Res] 2019 Oct; Vol. 212, pp. 89-103. Date of Electronic Publication: 2019 Jul 09.
DOI:	10.1016/j.trsl.2019.07.001
Abstrakt:	Prostate cancer (PCa) is one of the most common cancers types among men. Development and progression of PCa is associated with aberrant expression of oncogenic splicing-variants (eg, AR-v7), suggesting that dysregulation of the splicing process might represent a potential actionable target for PCa. Expression levels (mRNA and protein) of SF3B1, one of the main components of the splicing machinery, were analyzed in different cohorts of PCa patients (clinically localized [n = 84], highly aggressive PCa [n = 42], and TCGA dataset [n = 497]). Functional and mechanistic assays were performed in response to pladienolide-B in nontumor and tumor-derived prostate cells. Our results revealed that SF3B1 was overexpressed in PCa tissues and its levels were associated with clinically relevant PCa-aggressive features (eg, metastasis/AR-v7 expression). Moreover, inhibition of SF3B1 activity by pladienolide-B reduced functional parameters of aggressiveness (proliferation/migration/tumorspheres-formation/apoptosis) in PCa cell lines, irrespective of AR-v7 expression, and reduced viability of primary PCa cells. Antitumor actions of pladienolide-B involved: (1) inhibition of PI3K/AKT and JNK signaling pathways, (2) modulation of tumor markers and splicing variants (AR-v7/In1-ghrelin), and (3) regulation of key components of mRNA homeostasis-associated machineries (spliceosome/SURF/EJC). Altogether, our results demonstrated that SF3B1 is overexpressed and associated with malignant features in PCa, and its inhibition reduces PCa aggressiveness, suggesting that SF3B1 could represent a novel prognostic biomarker and a therapeutic target in PCa. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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