OncomiRs miR-106a and miR-17 negatively regulate the nucleoside-derived drug transporter hCNT1
Por:
Boces-Pascual, C, Mata A, Martin-Satue, M, Boix, L, Gironella, M, Pastor-Anglada M and Perez-Torras S
Publicada:
1 dic 2021
Ahead of Print:
1 oct 2021
Resumen:
High-affinity uptake of natural nucleosides as well as nucleoside derivatives used in anticancer therapies is mediated by human concentrative nucleoside transporters (hCNTs). hCNT1, the hCNT family member that specifically transports pyrimidines, is also a transceptor involved in tumor progression. In particular, oncogenesis appears to be associated with hCNT1 downregulation in some cancers, although the underlying mechanisms are largely unknown. Here, we sought to address changes in colorectal and pancreatic ductal adenocarcinoma-both of which are important digestive cancers-in the context of treatment with fluoropyrimidine derivatives. An analysis of cancer samples and matching non-tumoral adjacent tissues revealed downregulation of hCNT1 protein in both types of tumor. Further exploration of the putative regulation of hCNT1 by microRNAs (miRNAs), which are highly deregulated in these cancers, revealed a direct relationship between the oncomiRs miR-106a and miR-17 and the loss of hCNT1. Collectively, our findings provide the first demonstration that hCNT1 inhibition by these oncomiRs could contribute to chemoresistance to fluoropyrimidine-based treatments in colorectal and pancreatic cancer.
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Filiaciones:
Boces-Pascual, C:
Molecular Pharmacology and Experimental Therapeutics, Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine, University of Barcelona (IBUB), Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER EHD), Instituto de Salud Carlos III, Madrid, Spain
Institut de Recerca Sant Joan de Déu (IR SJD-CERCA), Esplugues de Llobregat, Barcelona, Spain
Mata A:
Molecular Pharmacology and Experimental Therapeutics, Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine, University of Barcelona (IBUB), Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER EHD), Instituto de Salud Carlos III, Madrid, Spain
Institut de Recerca Sant Joan de Déu (IR SJD-CERCA), Esplugues de Llobregat, Barcelona, Spain
Martin-Satue, M:
Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Campus of Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain
Biomedical Research Institute of Bellvitge (IDIBELL), Oncobell Program, L'Hospitalet de Llobregat, Barcelona, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Boix, L:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER EHD), Instituto de Salud Carlos III, Madrid, Spain
Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic per a la Recerca Biomèdica (FCRB), University of Barcelona, Barcelona, Spain
Gironella, M:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER EHD), Instituto de Salud Carlos III, Madrid, Spain
Gastrointestinal & Pancreatic Oncology Group, Hospital Clinic of Barcelona/Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Pastor-Anglada M:
Molecular Pharmacology and Experimental Therapeutics, Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine, University of Barcelona (IBUB), Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER EHD), Instituto de Salud Carlos III, Madrid, Spain
Institut de Recerca Sant Joan de Déu (IR SJD-CERCA), Esplugues de Llobregat, Barcelona, Spain
Perez-Torras S:
Molecular Pharmacology and Experimental Therapeutics, Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine, University of Barcelona (IBUB), Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER EHD), Instituto de Salud Carlos III, Madrid, Spain.
Institut de Recerca Sant Joan de Déu (IR SJD-CERCA), Esplugues de Llobregat, Barcelona, Spain.
Green Published, hybrid
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