Loss of Setd2 promotes Kras-induced acinar-to-ductal metaplasia and epithelia-mesenchymal transition during pancreatic carcinogenesis.

Acinar Cells / pathology Animals Carcinoma, Pancreatic Ductal / genetics Disease Models, Animal Epithelial-Mesenchymal Transition / genetics Histone-Lysine N-Methyltransferase / genetics Metaplasia / genetics Mice Mice, Knockout Mutation / genetics Pancreatic Neoplasms / genetics Proto-Oncogene Proteins p21(ras) / physiology
cancer genetics pancreatic cancer

Journal

Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R

Informations de publication

Date de publication:
04 2020
Historique:
received: 24 01 2019
revised: 18 06 2019
accepted: 30 06 2019
pubmed: 14 7 2019
medline: 24 10 2020
entrez: 14 7 2019
Statut: ppublish

Résumé

SETD2, the sole histone H3K36 trimethyltransferase, is frequently mutated or deleted in human cancer, including pancreatic ductal adenocarcinoma (PDAC). However, whether SETD2/H3K36me3 alteration results in PDAC remains largely unknown. TCGA(PAAD) public database and PDAC tissue array with SETD2/H3K36me3 staining were used to investigate the clinical relevance of SETD2 in PDAC. Furthermore, to define the role of SETD2 in the carcinogenesis of PDAC, we crossed conditional Setd2 knockout mice ( SETD2 mutant/low expression was correlated with poor prognosis in patients with PDAC. Next, we found that Setd2 acted as a putative tumour suppressor in Kras-driven pancreatic carcinogenesis. Mechanistically, Together, our findings highlight the function of SETD2 during pancreatic carcinogenesis, which would advance our understanding of epigenetic dysregulation in PDAC. Moreover, it may also pave the way for development of targeted, patients-tailored therapies for PDAC patients with SETD2 deficiency.

Identifiants

DOI: 10.1136/gutjnl-2019-318362 PMID: 31300513
pubmed: 31300513
pii: gutjnl-2019-318362
doi: 10.1136/gutjnl-2019-318362
doi:

Substances chimiques

Histone-Lysine N-Methyltransferase EC 2.1.1.43
SETD2 protein, mouse EC 2.1.1.43
Hras protein, mouse EC 3.6.5.2
Proto-Oncogene Proteins p21(ras) EC 3.6.5.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

715-726

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Ningning Niu (N)

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Ping Lu (P)

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Yanlin Yang (Y)

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Ruizhe He (R)

Department of Biliary-Pancreatic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Li Zhang (L)

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Juanjuan Shi (J)

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Jinghua Wu (J)

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Minwei Yang (M)

Department of Biliary-Pancreatic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Zhi-Gang Zhang (ZG)

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
ORCID: 0000-0001-8965-223X

Li-Wei Wang (LW)

Department of Oncology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.

Wei-Qiang Gao (WQ)

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.

Aida Habtezion (A)

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA.
ORCID: 0000-0002-4473-006X

Gary Guishan Xiao (GG)

School of pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China.

Yongwei Sun (Y)

Department of Biliary-Pancreatic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.
ORCID: 0000-0002-5937-634X

Li Li (L)

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.

Jing Xue (J)

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.
ORCID: 0000-0002-6497-1792

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules acineuses › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Eucaryotes › Animaux › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Carcinome du canal pancréatique › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transdifférenciation cellulaire › Transition épithélio-mésenchymateuse › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › Protein Methyltransferases › Histone méthyltransférases › Histone-lysine N-methyltransferase › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Métaplasie › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Loss of Setd2 promotes Kras-induced...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes p21(ras) › Loss of Setd2 promotes Kras-induced...