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Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage.
Carotenuto, Pietro; Amato, Francesco; Lampis, Andrea; Rae, Colin; Hedayat, Somaieh; Previdi, Maria C; Zito, Domenico; Raj, Maya; Guzzardo, Vincenza; Sclafani, Francesco; Lanese, Andrea; Parisi, Claudia; Vicentini, Caterina; Said-Huntingford, Ian; Hahne, Jens C; Hallsworth, Albert; Kirkin, Vladimir; Young, Kate; Begum, Ruwaida; Wotherspoon, Andrew; Kouvelakis, Kyriakos; Azevedo, Sergio Xavier; Michalarea, Vasiliki; Upstill-Goddard, Rosie; Rao, Sheela; Watkins, David; Starling, Naureen; Sadanandam, Anguraj; Chang, David K; Biankin, Andrew V; Jamieson, Nigel B; Scarpa, Aldo; Cunningham, David; Chau, Ian; Workman, Paul; Fassan, Matteo; Valeri, Nicola; Braconi, Chiara.
Afiliación
  • Carotenuto P; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
  • Amato F; TIGEM - Telethon Institute of Genetics and Medicine, Naples, Italy.
  • Lampis A; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Rae C; Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
  • Hedayat S; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Previdi MC; Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
  • Zito D; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
  • Raj M; Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
  • Guzzardo V; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
  • Sclafani F; Department of Medicine, University of Padua, Padua, Italy.
  • Lanese A; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Parisi C; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Vicentini C; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Said-Huntingford I; ARC-Net Research Centre and Department of Diagnostics and Public Health, Section of Pathology, , University of Verona, Verona, Italy.
  • Hahne JC; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
  • Hallsworth A; Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
  • Kirkin V; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
  • Young K; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
  • Begum R; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Wotherspoon A; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Kouvelakis K; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Azevedo SX; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Michalarea V; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Upstill-Goddard R; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Rao S; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Watkins D; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Starling N; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Sadanandam A; The Royal Marsden NHS Trust, London and Surrey, London, UK.
  • Chang DK; Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
  • Biankin AV; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Jamieson NB; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK.
  • Scarpa A; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Cunningham D; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK.
  • Chau I; South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW, Australia.
  • Workman P; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Fassan M; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK.
  • Valeri N; ARC-Net Research Centre and Department of Diagnostics and Public Health, Section of Pathology, , University of Verona, Verona, Italy.
  • Braconi C; The Royal Marsden NHS Trust, London and Surrey, London, UK.
Nat Commun ; 12(1): 6738, 2021 11 18.
Article en En | MEDLINE | ID: mdl-34795259
ABSTRACT
FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Daño del ADN / Protocolos de Quimioterapia Combinada Antineoplásica / Regulación Neoplásica de la Expresión Génica / Carcinoma Ductal Pancreático / MicroARNs Tipo de estudio: Diagnostic_studies / Prognostic_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Daño del ADN / Protocolos de Quimioterapia Combinada Antineoplásica / Regulación Neoplásica de la Expresión Génica / Carcinoma Ductal Pancreático / MicroARNs Tipo de estudio: Diagnostic_studies / Prognostic_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido