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MiR-378a inhibits glucose metabolism by suppressing GLUT1 in prostate cancer.
Cannistraci, A; Hascoet, P; Ali, A; Mundra, P; Clarke, N W; Pavet, V; Marais, R.
Afiliación
  • Cannistraci A; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
  • Hascoet P; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
  • Ali A; Genito-Urinary Cancer Research Group and the FASTMAN Prostate Cancer Centre for Excellence, Division of Cancer Sciences, Manchester Cancer Research Centre, The University of Manchester, 555 Wilmslow Road, Manchester, M20 4GJ, UK.
  • Mundra P; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
  • Clarke NW; Genito-Urinary Cancer Research Group and the FASTMAN Prostate Cancer Centre for Excellence, Division of Cancer Sciences, Manchester Cancer Research Centre, The University of Manchester, 555 Wilmslow Road, Manchester, M20 4GJ, UK.
  • Pavet V; The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK.
  • Marais R; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK. valeria.pavet@cruk.manchester.ac.uk.
Oncogene ; 41(10): 1445-1455, 2022 03.
Article en En | MEDLINE | ID: mdl-35039635
Prostate cancer (PCa) is the fifth leading cause of cancer related deaths worldwide, in part due to a lack of molecular stratification tools that can distinguish primary tumours that will remain indolent from those that will metastasise. Amongst potential molecular biomarkers, microRNAs (miRs) have attracted particular interest because of their high stability in body fluids and fixed tissues. These small non-coding RNAs modulate several physiological and pathological processes, including cancer progression. Herein we explore the prognostic potential and the functional role of miRs in localised PCa and their relation to nodal metastasis. We define a 7-miR signature that is associated with poor survival independently of age, Gleason score, pathological T state, N stage and surgical margin status and that is also prognostic for disease-free survival in patients with intermediate-risk localised disease. Within our 7-miR signature, we show that miR-378a-3p (hereafter miR-378a) levels are low in primary tumours compared to benign prostate tissue, and also lower in Gleason score 8-9 compared to Gleason 6-7 PCa. We demonstrate that miR-378a impairs glucose metabolism and reduces proliferation in PCa cells through independent mechanisms, and we identify glucose transporter 1 (GLUT1) messenger RNA as a direct target of miR-378a. We show that GLUT1 inhibition hampers glycolysis, leading to cell death. Our data provides a rational for a new PCa stratification strategy based on miR expression, and it reveals that miR-378a and GLUT1 are potential therapeutic targets in highly aggressive glycolytic PCa.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / MicroARNs Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / MicroARNs Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido