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

Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage

Pietro Carotenuto, Francesco Amato, Andrea Lampis, Colin Rae, Somaieh Hedayat, Maria C. Previdi, Domenico Zito, Maya Raj, Vincenza Guzzardo, Francesco Sclafani, Andrea Lanese, Claudia Parisi, Caterina Vicentini, Ian Said-Huntingford, Jens C. Hahne, Albert Hallsworth, Vladimir Kirkin, Kate Young, Ruwaida Begum, Andrew Wotherspoon, Kyriakos Kouvelakis, Sergio Xavier Azevedo, Vasiliki Michalarea, Rosie Upstill-Goddard, Sheela Rao, David Watkins, Naureen Starling, Anguraj Sadanandam, David K. Chang, Andrew V. Biankin, Nigel B. Jamieson, Aldo Scarpa, David Cunningham, Ian Chau, Paul Workman, Matteo Fassan, Nicola Valeri and Chiara Braconi ()
Additional contact information
Pietro Carotenuto: The Institute of Cancer Research
Francesco Amato: University of Glasgow
Andrea Lampis: The Institute of Cancer Research
Colin Rae: University of Glasgow
Somaieh Hedayat: The Institute of Cancer Research
Maria C. Previdi: The Institute of Cancer Research
Domenico Zito: The Institute of Cancer Research
Maya Raj: The Institute of Cancer Research
Vincenza Guzzardo: University of Padua
Francesco Sclafani: The Royal Marsden NHS Trust, London and Surrey
Andrea Lanese: The Royal Marsden NHS Trust, London and Surrey
Claudia Parisi: The Royal Marsden NHS Trust, London and Surrey
Caterina Vicentini: , University of Verona
Ian Said-Huntingford: The Institute of Cancer Research
Jens C. Hahne: The Institute of Cancer Research
Albert Hallsworth: The Institute of Cancer Research
Vladimir Kirkin: The Institute of Cancer Research
Kate Young: The Royal Marsden NHS Trust, London and Surrey
Ruwaida Begum: The Royal Marsden NHS Trust, London and Surrey
Andrew Wotherspoon: The Royal Marsden NHS Trust, London and Surrey
Kyriakos Kouvelakis: The Royal Marsden NHS Trust, London and Surrey
Sergio Xavier Azevedo: The Royal Marsden NHS Trust, London and Surrey
Vasiliki Michalarea: The Royal Marsden NHS Trust, London and Surrey
Rosie Upstill-Goddard: University of Glasgow
Sheela Rao: The Royal Marsden NHS Trust, London and Surrey
David Watkins: The Royal Marsden NHS Trust, London and Surrey
Naureen Starling: The Royal Marsden NHS Trust, London and Surrey
Anguraj Sadanandam: The Institute of Cancer Research
David K. Chang: University of Glasgow
Andrew V. Biankin: University of Glasgow
Nigel B. Jamieson: University of Glasgow
Aldo Scarpa: , University of Verona
David Cunningham: The Royal Marsden NHS Trust, London and Surrey
Ian Chau: The Royal Marsden NHS Trust, London and Surrey
Paul Workman: The Institute of Cancer Research
Matteo Fassan: University of Padua
Nicola Valeri: The Institute of Cancer Research
Chiara Braconi: The Institute of Cancer Research

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27099-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27099-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27099-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().