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Start Over Topic gene expression regulation, neoplastic
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1. A novel microRNA-based signature predicts prognosis among nasopharyngeal cancer patients.

Author

Wang T, Wu J, Wu Y, Cheng Y, Deng Y, Liao J, Liu H, and Peng H

Subjects
Area Under Curve, Humans, Kaplan-Meier Estimate, MicroRNAs metabolism, Nasopharyngeal Neoplasms pathology, Prognosis, Reproducibility of Results, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, MicroRNAs genetics, Nasopharyngeal Neoplasms genetics
Abstract

Impact Statement: Nasopharyngeal cancer is one of the most common malignant tumors in the head and neck. Identification of promising miRNA biomarkers might benefit a lot to the detection of nasopharyngeal carcinoma. A three-miRNA signature (has-miR-142-3p, has-miR-29c, and has-miR-30e) was obviously associated with the overall survival of nasopharyngeal carcinoma patients. The model has better clinical independence and has better clinical prediction effect when combined with clinical characteristics. Our results revealed that a three-miRNA signature was a potential novel prognostic biomarker for nasopharyngeal carcinoma.

Published
2021
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2. Genetic screens reveal mechanisms for the transcriptional regulation of tissue-specific genes in normal cells and tumors

Author

Morgane Bourmaud, Anda Huna, Ikrame Naciri, Marthe Laisné, Pierre-Antoine Defossez, Selene Di Carlo, Nikhil Gupta, David Bernard, Lucie Peduto, Laure Ferry, Olivier Kirsh, Nadine Martin, Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stroma, inflammation et réparation tissulaire - Stroma, Inflammation and Tissue Repair, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), National Institutes of Health [EpiCALC 2013 to P.A.D. and D.B.], Institut National du Cancer [PLBio15–013 to P.A.D. and D.B.], Labex ‘Who am I?’ [ANR-11-LABX-0071 under ANR-11-IDEX-005–02, to P.A.D.], European Research Council [ERC648428-PERIF to L.P.], Fondation ARC [4th-year PhD scholarship to I.N., Programme Labellisé PGA1/RF20180206807 to P.A.D.], Fondation pour la Recherche Médicale [postdoctoral fellowship to A.H.]. The open access publication charge for this paper has been waived by Oxford University Press - NAR Editorial Board members are entitled to one free paper per year in recognition of their work on behalf of the journal., The authors thanks the Genomics Platform of Institut Curie for Nanostring analysis. The Nanostring platform of Institut Curie was initiated with the support of French grants (LabEx and EquipEx): ANR-10-IDEX-0001–02 PSL, ANR-11-LBX-0044 and « INCa-DGOS- 4654 » SIRIC11–002. We thank Valérie Doye, Stéphanie Bolhy, and Philippe Girard at Institut Jacques Monod for help with the Incucyte. Concerning the lentiviral vector production, we acknowledge Christophe Huret and the Paris Diderot Vectorology Platform of Paris Diderot University, Sorbonne Paris Cité, CNRS UMR 7216, Paris, France. We acknowledge the kind help of Elisabeth Brambilla with some experiments that do not appear in the submitted version of the manuscript. For the gift of reagents we acknowledge the kind contribution of Katrin Chua, Philippe Chavrier, Annabelle Decottignies, Sébastien Jauliac and Michael Kracht. Finally, we thank the following colleagues for useful discussions: Jean-Marc Vanacker, Robert Dante, Nathalie Théret, Saadi Khochbin, Céline Prunier, Céline Vallot, Claire Rougeulle, Isabelle Bernard-Pierrot, Slimane Ait-si-ali, Jonathan Weitzman, Valérie Lallemand-Mezger, ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), European Project: 648428,H2020,ERC-2014-CoG,PERIF(2015), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM), Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École pratique des hautes études (EPHE), Centre de Recherche en Cancérologie de Lyon (CRCL), Stroma, inflammation et réparation tissulaire, ATMEL [Rousset], Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), TOMASSO DEVERGE, Carina, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, and Perivascular cells at the crossroads of inflammation, regeneration and fibrosis - PERIF - - H20202015-11-01 - 2020-10-31 - 648428 - VALID

Subjects
Transcription, Genetic, [SDV]Life Sciences [q-bio], ADAM12 Protein, Triple Negative Breast Neoplasms, Biology, Protein Serine-Threonine Kinases, Cell Line, Transforming Growth Factor beta1, 03 medical and health sciences, 0302 clinical medicine, RNA interference, Cell Line, Tumor, Neoplasms, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, Genetics, Humans, Epigenetics, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Histone Acetyltransferases, Regulation of gene expression, 0303 health sciences, Gene regulation, Chromatin and Epigenetics, Chromatin, Cell biology, Gene Expression Regulation, Neoplastic, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Organ Specificity, Cancer cell, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA Interference, 030217 neurology & neurosurgery, Genetic screen, Signal Transduction
Abstract

International audience; The proper tissue-specific regulation of gene expression is essential for development and homeostasis in metazoans. However, the illegitimate expression of normally tissue-restricted genes-like testis- or placenta-specific genes-is frequently observed in tumors; this promotes transformation, but also allows immunotherapy. Two important questions are: how is the expression of these genes controlled in healthy cells? And how is this altered in cancer? To address these questions, we used an unbiased approach to test the ability of 350 distinct genetic or epigenetic perturbations to induce the illegitimate expression of over 40 tissue-restricted genes in primary human cells. We find that almost all of these genes are remarkably resistant to reactivation by a single alteration in signaling pathways or chromatin regulation. However, a few genes differ and are more readily activated; one is the placenta-expressed gene ADAM12, which promotes invasion. Using cellular systems, an animal model, and bioinformatics, we find that a non-canonical but druggable TGF-β/KAT2A/TAK1 axis controls ADAM12 induction in normal and cancer cells. More broadly, our data show that illegitimate gene expression in cancer is an heterogeneous phenomenon, with a few genes activatable by simple events, and most genes likely requiring a combination of events to become reactivated.

Published
2019

3. p53 regulates epithelial–mesenchymal transition through microRNAs targeting ZEB1 and ZEB2

Author

Young-Jun Jeon, Flavia Pichiorri, Angelo Veronese, Pascal Pineau, Anne Dejean, Tae Jin Lee, Hansjuerg Alder, Agnès Marchio, Stefano Volinia, Taewan Kim, Jeff Palatini, Chang Gong Liu, Sung Suk Suh, Carlo M. Croce, Comprehensive Cancer Center [Colombus], Ohio State University [Columbus] (OSU), Molecular, Cellular, and Developmental Biology Program [Columbus] (MCDB), Organisation Nucléaire et Oncogenèse, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was funded by National Cancer Institute grant RC2 CA148302., We thank Dr. B. Vogelstein for p53+/+ and p53−/− RKO cells, Dr. Gustavo Leone for p53+/+ and p53−/− MEFs, Dr. Gregory J. Goodall for pCIneo-hRL-ZEB1/2 constructs, and Dr. Anders H. Lund for pcDNA3-Zeb2-HA constructs. We also thank Dr. Kay Huebner (The Ohio State University), Dr. Thomas D. Schmittgen (The Ohio State University), and Susan Lutz for careful editing of this paper, and Sharon Palko and Dorothee Wernicke-Jameson for the administrative support., Pineau, Pascal, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Zinc Finger E-box-Binding Homeobox 1, genetics/metabolism, biosynthesis/genetics, Metastasis, genetics/metabolism/pathology, 0302 clinical medicine, MESH: Liver Neoplasms, Immunology and Allergy, genetics, RNA, Neoplasm, Neoplasm Metastasis, MESH: Carcinoma, Hepatocellular, MESH: Tumor Suppressor Protein p53, 0303 health sciences, digestive, oral, and skin physiology, Liver Neoplasms, Hep G2 Cells, MESH: Gene Expression Regulation, Neoplastic, MESH: Transcription Factors, Gene Expression Regulation, Neoplastic, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, embryonic structures, Female, Transcriptional Activation, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Immunology, Repressor, MESH: Hep G2 Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, MESH: Gene Expression Profiling, [SDV.CAN] Life Sciences [q-bio]/Cancer, microRNA, MESH: Homeodomain Proteins, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epithelial–mesenchymal transition, Transcription factor, Zinc Finger E-box Binding Homeobox 2, 030304 developmental biology, MESH: Zinc Finger E-box Binding Homeobox 2, Homeodomain Proteins, Neoplastic, MESH: Humans, Gene Expression Profiling, Carcinoma, Brief Definitive Report, Zinc Finger E-box-Binding Homeobox 1, Hepatocellular, Cell Biology, HCCS, medicine.disease, MESH: RNA, Neoplasm, MESH: Neoplasm Metastasis, MESH: Male, Repressor Proteins, Gene expression profiling, MicroRNAs, MESH: Epithelial-Mesenchymal Transition, Gene Expression Regulation, Tumor progression, Cancer research, RNA, Neoplasm, MESH: Transcriptional Activation, genetics/metabolism/pathology, Epithelial-Mesenchymal Transition, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hep G2 Cells, Homeodomain Proteins, biosynthesis/genetics, Humans, Liver Neoplasms, genetics/metabolism/pathology, Male, MicroRNAs, genetics/metabolism, Neoplasm Metastasis, RNA, genetics/metabolism, Repressor Proteins, biosynthesis/genetics, Transcription Factors, biosynthesis/genetics, Transcriptional Activation, genetics, Tumor Suppressor Protein p53, Tumor Suppressor Protein p53, MESH: Female, MESH: MicroRNAs, 030215 immunology, Transcription Factors
Abstract

By transactivating expression of miRNAs that repress expression of the ZEB1 and ZEB2 transcription factors, p53 inhibits the epithelial–mesenchymal transition., p53 suppresses tumor progression and metastasis. Epithelial–mesenchymal transition (EMT) is a key process in tumor progression and metastasis. The transcription factors ZEB1 and ZEB2 promote EMT. Here, we show that p53 suppresses EMT by repressing expression of ZEB1 and ZEB2. By profiling 92 primary hepatocellular carcinomas (HCCs) and 9 HCC cell lines, we found that p53 up-regulates microRNAs (miRNAs), including miR-200 and miR-192 family members. The miR-200 family members transactivated by p53 then repress ZEB1/2 expression. p53-regulated miR-192 family members also repress ZEB2 expression. Inhibition or overexpression of the miRNAs affects p53-regulated EMT by altering ZEB1 and ZEB2 expression. Our findings indicate that p53 can regulate EMT, and that p53-regulated miRNAs are critical mediators of p53-regulated EMT.

Published
2011