Posttranscriptional Regulation of PER1 Underlies the Oncogenic Function of IRE
| Autor: | Arisa Higa, Raphael Pineau, Michael Hallett, Stéphanie Lhomond, Olivier Pluquet, Marion Bouchecareilh, Anne Vital, Sandrine Loriot, Gaelle Cubel, Jann N. Sarkaria, Maylis Delugin, Hugues Loiseau, Wenting Wu, Nicolas Dejeans, Keith Anderson, Sara J. C. Gosline, Frédéric Saltel, Martin E. Fernandez-Zapico, Fausto J. Rodriguez, C. Combe, Jean Rosenbaum, Eric Chevet, Nathalie Dugot-Senant, Saïd Taouji |
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| Přispěvatelé: | Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), DIPI (DIPI), ENISE, Ecosystèmes aquatiques et changements globaux (UR EABX), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Centre de Recherche sur la Matière Divisée (CRMD), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Department of Health and Human Services, National Institutes of Health [Bethesda] (NIH), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), This work was supported by an Avenir program (INSERM), grants from the Institut National du Cancer (INCa), Ligue contre le cancer, a Marie Curie International Reintegration Grant (E. Chevet), a grant from the Mayo Clinic Cancer Centre (M.E. Fernandez-Zapico), a grant from Institut Fédératif de Recherche 66 (O. Pluquet). O. Pluquet was supported by fellowships from INSERM and Association pour la Recherche contre le Cancer. M. Bouchecareilh was supported from a fellowship from le Conseil Régional d'Aquitaine and la Fondation pour la Recherche Française (FRM). Human glioblastoma samples were collected through the Bordeaux Tumor Bank (JP Merlio, CHU Bordeaux, France) funded by the Cancéropôle Grand Sud-Ouest and by a CEREPEG project grant (PHRC 2003, H. Loiseau) or through the Mayo Clinic Department of Clinical Pathology and funded by the Mayo Clinic SPORE in Brain Cancer P50 CA108961 (Rochester)., The authors thank M. Moenner (Université Bordeaux 1, Bordeaux, France) for precious help and fruitful discussions, S. Manié (UMR CNRS 5286, INSERM 1052, Cancer Research Center of Lyon, Lyon, France), and the Chevet lab for critical reading of the manuscript. The authors also thank Dr S. Gery (University of California, Los Angeles, CA) for the gift of pcDNA3.1-hPER1 expression vector and Dr U. Albrecht (Freiburg, Switzerland) for providing us with the pPER1-Luc vector., Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Diagnostics et imageries des procédés industriels (ENISE-DIPI), Ecole Nationale d'Ingénieurs de Saint Etienne (ENISE), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Endoribonuclease activity [SDV]Life Sciences [q-bio] Circadian clock MESH: Base Sequence MESH: Period Circadian Proteins/metabolism Mice 0302 clinical medicine RNA interference MESH: Glioblastoma/metabolism MESH: Reverse Transcriptase Polymerase Chain Reaction MESH: Animals RNA Processing Post-Transcriptional MESH: Gene Expression Regulation Neoplastic/physiology Oligonucleotide Array Sequence Analysis Regulation of gene expression 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Period Circadian Proteins MESH: Protein-Serine-Threonine Kinases/genetics Cell biology Gene Expression Regulation Neoplastic Oncology MESH: Endoribonucleases/metabolism 030220 oncology & carcinogenesis MESH: Glioblastoma/genetics RNA Interference PER1 MESH: RNA Processing Post-Transcriptional endocrine system MESH: Xenograft Model Antitumor Assays XBP1 Molecular Sequence Data MESH: RNA Interference MESH: Endoribonucleases/genetics [SDV.CAN]Life Sciences [q-bio]/Cancer Protein Serine-Threonine Kinases Biology Transfection Article 03 medical and health sciences Endoribonucleases MESH: Unfolded Protein Response/physiology Animals Humans Gene silencing MESH: Protein-Serine-Threonine Kinases/metabolism RNA Messenger MESH: Mice 030304 developmental biology MESH: RNA Messenger MESH: Period Circadian Proteins/genetics MESH: Humans MESH: Molecular Sequence Data Base Sequence MESH: Transfection Xenograft Model Antitumor Assays Molecular biology MESH: Oligonucleotide Array Sequence Analysis Unfolded Protein Response Unfolded protein response Glioblastoma |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 2013, 73 (15), pp.4732-4743. ⟨10.1158/0008-5472.CAN-12-3989⟩ Cancer Research, 2013, 73 (15), pp.4732-4743. ⟨10.1158/0008-5472.CAN-12-3989⟩ |
| ISSN: | 0008-5472 1538-7445 |
| Popis: | Growing evidence supports a role for the unfolded protein response (UPR) in carcinogenesis; however, the precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified the circadian clock PER1 mRNA as a novel substrate of the endoribonuclease activity of the UPR sensor IRE1α. Analysis of the mechanism shows that IRE1α endoribonuclease activity decreased PER1 mRNA in tumor cells without affecting PER1 gene transcription. Inhibition of IRE1α signaling using either siRNA-mediated silencing or a dominant-negative strategy prevented PER1 mRNA decay, reduced tumorigenesis, and increased survival, features that were reversed upon PER1 silencing. Clinically, patients showing reduced survival have lower levels of PER1 mRNA expression and increased splicing of XBP1, a known IRE-α substrate, thereby pointing toward an increased IRE1α activity in these patients. Hence, we describe a novel mechanism connecting the UPR and circadian clock components in tumor cells, thereby highlighting the importance of this interplay in tumor development. Cancer Res; 73(15); 4732–43. ©2013 AACR. |
| Databáze: | OpenAIRE |
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