Distinct Regulation of EZH2 and its Repressive H3K27me3 Mark in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Journal of Investigative Dermatology Year : 2023

Distinct Regulation of EZH2 and its Repressive H3K27me3 Mark in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma

Marie-Alice Durand (1) , Aurélie Drouin (1) , Alice Mouchard (2, 1) , Laurine Durand (1) , Clara Esnault (1) , Patricia Berthon (1) , Anne Tallet (3) , Yannick Le Corre (4) , Ewa Hainaut-Wierzbicka (5) , Astrid Blom (6) , Philippe Saiag (6) , Nathalie Beneton (7) , Guido Bens (8) , Charlee Nardin (9) , François Aubin (9) , Monica Dinulescu (10) , Christine Collin (3) , Gaëlle Fromont-Hankard (3) , Bernard Cribier (11) , Sara Laurent-Roussel (12) , Kristof Cokelaere (13) , Roland Houben (14) , David Schrama (14) , Paul Peixoto (15, 16) , Eric Hervouet (15, 16) , Kamel Bachiri (17) , Diala Kantar (17) , Etienne Coyaud (17) , Serge Guyétant (18, 1) , Mahtab Samimi (2, 1) , Antoine Touzé (1) , Thibault Kervarrec (1, 18)
1 UMR ISP - Infectiologie et Santé Publique
2 Service de dermatologie (CHRU de Tours)
3 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
4 CHU Angers - Centre Hospitalier Universitaire d'Angers
5 CHU Poitiers - Centre hospitalier universitaire de Poitiers
6 Hôpital Ambroise Paré [AP-HP]
7 Service de dermatologie [CH Le Mans]
8 CHRO - Centre Hospitalier Régional d'Orléans
9 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
10 Centre Hospitalier Universitaire [Rennes]
11 CHU Strasbourg
12 Centre de Dermatopathologie de la Roquette
13 Jan Yperman Hospital
14 University Hospital of Würzburg
15 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
16 EPIGENExp - EPIgenetics and GENe EXPression Technical Plateform
17 PRISM - Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192
18 Service de Pathologie [CHRU Tours]
Marie-Alice Durand
Infectiologie et Santé Publique
Aurélie Drouin
Infectiologie et Santé Publique
Alice Mouchard
Service de dermatologie (CHRU de Tours)
Infectiologie et Santé Publique
Laurine Durand
Infectiologie et Santé Publique
Clara Esnault
Infectiologie et Santé Publique
Patricia Berthon
Infectiologie et Santé Publique
Anne Tallet
Centre Hospitalier Régional Universitaire de Tours
Yannick Le Corre
Centre Hospitalier Universitaire d'Angers
Ewa Hainaut-Wierzbicka
Centre hospitalier universitaire de Poitiers
Astrid Blom
Hôpital Ambroise Paré [AP-HP]
Philippe Saiag
Hôpital Ambroise Paré [AP-HP]
Nathalie Beneton
Service de dermatologie [CH Le Mans]
Guido Bens
  • Function : Author
Centre Hospitalier Régional d'Orléans
Charlee Nardin
Centre Hospitalier Régional Universitaire de Besançon
François Aubin
Centre Hospitalier Régional Universitaire de Besançon
Monica Dinulescu
Centre Hospitalier Universitaire [Rennes]
Christine Collin
Centre Hospitalier Régional Universitaire de Tours
Gaëlle Fromont-Hankard
Centre Hospitalier Régional Universitaire de Tours
Bernard Cribier
CHU Strasbourg
Sara Laurent-Roussel
Centre de Dermatopathologie de la Roquette
Kristof Cokelaere
Jan Yperman Hospital
Roland Houben
University Hospital of Würzburg
David Schrama
University Hospital of Würzburg
Paul Peixoto
Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
EPIgenetics and GENe EXPression Technical Plateform
Eric Hervouet
Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
EPIgenetics and GENe EXPression Technical Plateform
Kamel Bachiri
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192
Diala Kantar
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192
Etienne Coyaud
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192
Serge Guyétant
Service de Pathologie [CHRU Tours]
Infectiologie et Santé Publique
Mahtab Samimi
Service de dermatologie (CHRU de Tours)
Infectiologie et Santé Publique
Antoine Touzé
Infectiologie et Santé Publique
Thibault Kervarrec
  • Function : Correspondent author
  • PersonId : 1078201

Connectez-vous pour contacter l'auteur
Infectiologie et Santé Publique
Service de Pathologie [CHRU Tours]

Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer for which Merkel cell polyomavirus integration and expression of viral oncogenes small T and Large T have been identified as major oncogenic determinants. Recently, a component of the PRC2 complex, the histone methyltransferase enhancer of zeste homolog 2 (EZH2) that induces H3K27 trimethylation as a repressive mark has been proposed as a potential therapeutic target in MCC. Because divergent results have been reported for the levels of EZH2 and trimethylation of lysine 27 on histone 3, we analyzed these factors in a large MCC cohort to identify the molecular determinants of EZH2 activity in MCC and to establish MCC cell lines' sensitivity to EZH2 inhibitors. Immunohistochemical expression of EZH2 was observed in 92% of MCC tumors (156 of 170), with higher expression levels in virus-positive than virus-negative tumors (P = 0.026). For the latter, we showed overexpression of EZHIP, a negative regulator of the PRC2 complex. In vitro, ectopic expression of the large T antigen in fibroblasts led to the induction of EZH2 expression, whereas the knockdown of T antigens in MCC cell lines resulted in decreased EZH2 expression. EZH2 inhibition led to selective cytotoxicity on virus-positive MCC cell lines. This study highlights the distinct mechanisms of EZH2 induction between virus-negative and -positive MCC.

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Dermatology Cancer

Nathalie Katy Chanteloup  : Connect in order to contact the contributor

https://hal.inrae.fr/hal-04171482

Submitted on : Wednesday, July 26, 2023-2:27:40 PM

Last modification on : Thursday, July 27, 2023-3:57:43 AM

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hal-04171482 , version 1 (26-07-2023)

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Marie-Alice Durand, Aurélie Drouin, Alice Mouchard, Laurine Durand, Clara Esnault, et al.. Distinct Regulation of EZH2 and its Repressive H3K27me3 Mark in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma. Journal of Investigative Dermatology, 2023, ⟨10.1016/j.jid.2023.02.038⟩. ⟨hal-04171482⟩

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UNIV-TOURS UNIV-FCOMTE UNAM UNIV-LILLE INRAE INFECTIOLOGIE-SANTE-PUBLIQUE MICA-UNITES INRAEVALDELOIRE
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