MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma

Autor: David Meyronet, Emma Armandy, Priscillia Battiston-Montagne, Alain Jung, Sébastien Guihard, Julien Carras, Sonia Ledrappier, Marc Aubry, Ruth Rimokh, Sylvain Ferrandon, Delphine Poncet, Jean-Philippe Foy, Claire Rodriguez-Lafrasse, Pierre Saintigny, Nathalie Bonnin
Přispěvatelé: Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de Physique Nucléaire de Lyon (IPNL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Plateforme Génomique Santé Biogenouest®, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Jonchère, Laurent, Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Oncology
Male
Kaplan-Meier Estimate
HNSCC
NT5E
0302 clinical medicine
miR-422a
Medicine
Stage (cooking)
5'-Nucleotidase
ComputingMilieux_MISCELLANEOUS
Aged
80 and over
Middle Aged
3. Good health
Gene Expression Regulation
Neoplastic
Head and Neck Neoplasms
030220 oncology & carcinogenesis
Carcinoma
Squamous Cell
Female
RNA Interference
Research Paper
Adult
medicine.medical_specialty
[SDV.CAN]Life Sciences [q-bio]/Cancer
GPI-Linked Proteins
Cell Line
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
Downregulation and upregulation
Internal medicine
Cell Line
Tumor
microRNA
Cell Adhesion
Humans
Cell adhesion
Aged
Cell Proliferation
Oncogene
business.industry
Cell growth
medicine.disease
Head and neck squamous-cell carcinoma
Personalized medicine
MicroRNAs
030104 developmental biology
CD73
Neoplasm Recurrence
Local
business
Zdroj: Oncotarget
Oncotarget, 2016, 7 (28), pp.44023-44038. ⟨10.18632/oncotarget.9829⟩
Oncotarget, Impact journals, 2016, 7 (28), pp.44023-44038. ⟨10.18632/oncotarget.9829⟩
ISSN: 1949-2553
DOI: 10.18632/oncotarget.9829⟩
Popis: At the time of diagnosis, 60% of patients with head and neck squamous cell carcinoma (HNSCC) present tumors in an advanced stage (III-IV) of disease and 80% will relapse within the first two years post-treatment, due to their frequent radio(chemo)resistance. To identify new molecular targets and companion biomarkers, we have investigated the miRNome of 75 stage III-IV oropharynx tumors without relapse (R) or with loco-regional relapse (non-responder, NR) within two years post-treatment. Interestingly, miR-422a was significantly downregulated in NR tumors, in agreement with the increase in cell proliferation and adhesion induced by miR-422a inhibition in vitro. Furthermore, we identified CD73/NT5E oncogene as target of miR-422a. Indeed, modulation of the endogenous level of miR-422a inversely influences the expression and the enzymatic activity of CD73. Moreover, knocking down CD73 mimics the effects of miR-422a upregulation. Importantly, in tumors, miR-422a and CD73 expression levels are inversely correlated, and both are predictive of relapse free survival - especially considering loco(regional) recurrence - in vitro two independent cohorts of advanced oropharynx or HNSCC (N=255) tumors. In all, we reported, for the first time, that MiR-422a and its target CD73 are involved in early loco(regional) recurrence of HNSCC tumors and are new targets for personalized medicine.
Databáze: OpenAIRE
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