Upregulation of the tumor suppressor gene menin in hepatocellular carcinomas and its significance in fibrogenesis

Autor: Chang Xian Zhang, Bruno Turlin, Bruno Clément, Marie Bérangère Troadec, Antony Le Béchec, Olivier Loréal, Nathalie Théret, Katia Bourd-Boitin, Orlando Musso, Jean J. Leger, Dominique Bonnier, Pierre Zindy, Annie L'Helgoualc'h, Denise Glaise
Přispěvatelé: Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Détoxication et réparation tissulaire, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique moléculaire, signalisation et cancer (GMSC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Régulations des équilibres fonctionnels du foie normal et pathologique, Physiopathologie et pharmacologie cellulaires et moléculaires, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Rok vydání: 2006
Předmět:
Liver Cirrhosis
Microarray
polymerase chain reaction
MESH: Collagen Type I
HSC
multiple endocrine neoplasia type 1
NF-κB
MESH: Hepatocytes
0302 clinical medicine
suppression subtractive hybridization
MESH: Up-Regulation
Genes
Tumor Suppressor
HCC
MESH: Carcinoma
Hepatocellular
Oligonucleotide Array Sequence Analysis
hepatic stellate cell
nontumor
transforming growth factor beta
0303 health sciences
biology
hepatocellular carcinoma
Up-Regulation
PCR
MEN1
nuclear factor-kappaB
030220 oncology & carcinogenesis
reverse transcription quantitative polymerase chain reaction
MESH: Liver Cirrhosis
TGF-β
Carcinoma
Hepatocellular
Tumor suppressor gene
antisense
NT
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Transfection
Collagen Type I
03 medical and health sciences
Proto-Oncogene Proteins
MESH: Gene Library
Humans
RNA
Messenger
SSH
Gene
MESH: Transforming Growth Factor beta
Gene Library
MESH: RNA
Messenger
030304 developmental biology
MESH: Humans
Hepatology
MESH: Transfection
RT-qPCR
Transforming growth factor beta
MESH: Genes
Tumor Suppressor
Hepatic stellate cell activation
MESH: Proto-Oncogene Proteins
Suppression subtractive hybridization
MESH: Oligonucleotide Array Sequence Analysis
Hepatocytes
biology.protein
Cancer research
Hepatic stellate cell
AS
Zdroj: Hepatology
Hepatology, 2006, 44 (5), pp.1296-307. ⟨10.1002/hep.21367⟩
Hepatology, Wiley-Blackwell, 2006, 44 (5), pp.1296-307. ⟨10.1002/hep.21367⟩
ResearcherID
Publons
ISSN: 1527-3350
0270-9139
Popis: International audience; The molecular mechanisms underlying the progression of cirrhosis toward hepatocellular carcinoma were investigated by a combination of DNA microarray analysis and literature data mining. By using a microarray screening of suppression subtractive hybridization cDNA libraries, we first analyzed genes differentially expressed in tumor and nontumor livers with cirrhosis from 15 patients with hepatocellular carcinomas. Seventy-four genes were similarly recovered in tumor (57.8% of differentially expressed genes) and adjacent nontumor tissues (64% of differentially expressed genes) compared with histologically normal livers. Gene ontology analyses revealed that downregulated genes (n = 35) were mostly associated with hepatic functions. Upregulated genes (n = 39) included both known genes associated with extracellular matrix remodeling, cell communication, metabolism, and post-transcriptional regulation gene (e.g., ZFP36L1), as well as the tumor suppressor gene menin (multiple endocrine neoplasia type 1; MEN1). MEN1 was further identified as an important node of a regulatory network graph that integrated array data with array-independent literature mining. Upregulation of MEN1 in tumor was confirmed in an independent set of samples and associated with tumor size (P = .016). In the underlying liver with cirrhosis, increased steady-state MEN1 mRNA levels were correlated with those of collagen alpha2(I) mRNA (P < .01). In addition, MEN1 expression was associated with hepatic stellate cell activation during fibrogenesis and involved in transforming growth factor beta (TGF-beta)-dependent collagen alpha2(I) regulation. In conclusion, menin is a key regulator of gene networks that are activated in fibrogenesis associated with hepatocellular carcinoma through the modulation of TGF-beta response.
Databáze: OpenAIRE
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