Centre de Référence Maladies Rares

U1035 INSERM

Biotherapy of genetic diseases, inflammatory disorders and cancers (BMGIC)

FR: Biologie Fondamentale Appliquée à la Médecine

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miRCaDe team (MicroRNAs in Cancer and Development)
Project 5.1

Liver: pediatric (hepatoblastoma) and adult (hepatocellular carcinoma)

keywords: hepatoblastoma, hepatocellular carcinoma, Immuno-oncology, beta-catenine, metabolic adaptation

Description:

In this area of research, we have two main themes:

  • a.beta-catenin regulation, new oncogenic pathways and miRNA alterations in liver cancer.

Principal Investigator : C.F. Grosset, PhD, Inserm DR2
Workgroup members : P. Veschambre, PhD, Assist. Prof.; N. Mosca, PhD, Post-doc; A. Ghousein, PhD student.
Our interests consist in understanding the regulation of beta-catenin (CTNNB1), that control Wnt signaling, normal and pathological cell gene reprogramming, embryonic tissue development and tumorigenesis. Using RNA-seq technology, we are also looking at characterizing new pathway alterations (eg. Fanconi Anemia) and at identifying new molecular signatures (ex. TOP2A) specific of the aggressive and chemoresistant form of hepatoblastoma. Finally, we are investigating in details the role of miRNA:targets interaction network in liver carcinogenesis and tumor molecular signaling using integrative bioinformatics and state-of-the-art in vitro/in vivo techniques.

  • b. Immuno-oncology and metabolic adaptation.

Principal Investigator : A. Merched, PhD, Prof.
Workgroup members : V. Trezeguet-Busquet, PhD, CNRS CR1; M. Alannan, PhD student.
Our aim is to characterize the immunosuppressive mechanisms in the tumor microenvironment and the changes in lipid metabolism associated with tumorigenesis by combining molecular, cellular and in vivo approaches.

Related publications:

  • Tracking cellular and molecular changes in a species-specific manner during experimental hepatoblastoma progression in vivo Indersie E#, Hooks KB#, Capdevielle C, Fabre M, Dugot-Senant N, Desplat A, Lepreux S, Merched A, Grosset CF, Hagedorn M. # contributed equally Oncotarget (2018-03) 10.18632/oncotarget.24598
  • Role of O-glycanation and convertase maturation of the soluble Glypican-3 in inhibiting proliferation of hepatocellular carcinoma cells Saad A, Liet B, Joucla G, Santarelli X, Charpentier J, Claverol S, Grosset CF, Trézéguet V. Biochemistry (2018-02) 10.1021/acs.biochem.7b01208
  • New insights into diagnosis and therapeutic options for proliferative hepatoblastoma. Hooks KB, Audoux J, Fazli H, Lesjean S, Ernault T, Senant ND, Leste-Lasserre T, Hagedorn M, Rousseau B, Danet C, Branchereau S, Brugières L, Taque S, Guettier C, Fabre M, Rullier A, Buendia MA, Commes T, Grosset CF*, Raymond AA*. * co-last authors. Hepatology (2017-11) 10.1002/hep.29672
  • SimBA: A methodology and tools for evaluating the performance of RNA-Seq bioinformatic pipelines. Audoux J, Salson M, Grosset CF, Beaumeunier S, Holder JM, Commes T, Philippe N. BMC Bioinformatics (2017-09) PMC5623974
  • New tumor suppressor microRNAs target glypican-3 in human liver cancer. Cartier F, Indersie E, Lesjean S, Charpentier J, Hooks KB, Ghousein A, Desplat A, Dugot-Senant N, Trézéguet V, Sagliocco F, Hagedorn M, Grosset CF. Oncotarget (2017-06) PMC5522324
  • MicroRNA Therapy Inhibits Hepatoblastoma Growth In Vivo by Targeting b -Catenin and Wnt Signaling Emilie Indersie, Sarah Lesjean, Katarzyna B. Hooks , Francis Sagliocco, Tony Ernault, Stefano Cairo, Maria Merched-Sauvage, Anne Rullier, Brigitte Le Bail, Sophie Taque, Michael Grotzer, Sophie Branchereau, Catherine Guettier, Monique Fabre, Laurence Brugières, Martin Hagedorn, Marie-Annick Buendia, and Christophe F. Grosset Hepatology Communications (2017-04) onlinelibrary.wiley.com/doi/10.1
  • MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression. Maurel M, Dejeans N, Taouji S, Chevet E, Grosset CF. RNA (2013-06) PMC3683912
  • A functional screening identifies five microRNAs controlling glypican-3: role of miR-1271 down-regulation in hepatocellular carcinoma. Maurel M, Jalvy S, Ladeiro Y, Combe C, Vachet L, Sagliocco F, Bioulac-Sage P, Pitard V, Jacquemin-Sablon H, Zucman-Rossi J, Laloo B, Grosset CF. Hepatology (2013-01) janv 2013 PMID : 22865282
  • Molecular basis of differential target regulation by miR-96 and miR-182: the Glypican-3 as a model. Jalvy-Delvaille S, Maurel M, Majo V, Pierre N, Chabas S, Combe C, Rosenbaum J, Sagliocco F, Grosset CF. Nucleic Acids Res (2012-02) fev 2012. PMID: 22009679

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INSERM U1035! - University of Bordeaux
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Work +33 557 57 13 73/74
sarah.lesjean@inserm.fr