Carbohydrate response element binding protein (ChREBP) correlates with colon cancer progression and contributes to cell proliferation.

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics Biomarkers, Tumor Carbohydrate Metabolism Cell Cycle Checkpoints Cell Proliferation Colonic Neoplasms / etiology Disease Progression Disease Susceptibility Gene Expression Regulation, Neoplastic Glycolysis Humans Lipogenesis Male Signal Transduction Tumor Suppressor Protein p53 / metabolism

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
06 03 2020
Historique:
received: 13 06 2019
accepted: 07 02 2020
entrez: 8 3 2020
pubmed: 8 3 2020
medline: 24 11 2020
Statut: epublish

Résumé

Cancers are characterized by reprogrammed glucose metabolisms to fuel cell growth and proliferation. Carbohydrate response element binding protein (ChREBP) is a glucose-mediated transcription factor that strongly regulates glycolytic and lipogenic pathways. It has been shown to associate with metabolic diseases, such as obesity, diabetes and non-alcoholic fatty liver diseases. However, how it associates with cancers has not been well understood. In this study, ChREBP expression was assessed by immunohistochemistry in colon tissue arrays containing normal colon tissue and cancer tissue at different clinical stages. Tissue mRNA levels of ChREBP were also measured in a cohort of colon cancer patients. We found that ChREBP mRNA and protein expression were significantly increased in colon cancer tissue compared to healthy colon (p < 0.001), and their expression was positively correlated to colon malignancy (for mRNA, p = 0.002; for protein p < 0.001). Expression of lipogenic genes (ELOVL6 and SCD1) in colon cancer was also positively associated with colon malignancy (for both genes, p < 0.001). In vitro, ChREBP knockdown with siRNA transfection inhibited cell proliferation and induced cell cycle arrest without changes in apoptosis in colon cancer cell lines (HT29, DLD1 and SW480). Glycolytic and lipogenic pathways were inhibited but the p53 pathway was activated after ChREBP knockdown. Taken together, ChREBP expression is associated with colon malignancy and it might contribute to cell proliferation via promoting anabolic pathways and inhibiting p53. In addition, ChREBP might represent a novel clinical useful biomarker to evaluate the malignancy of colon cancer.

Identifiants

DOI: 10.1038/s41598-020-60903-9 PMID: 32144313 PMC: PMC7060312
pubmed: 32144313
doi: 10.1038/s41598-020-60903-9
pii: 10.1038/s41598-020-60903-9
pmc: PMC7060312
doi:

Substances chimiques

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors 0
Biomarkers, Tumor 0
MLXIPL protein, human 0
Tumor Suppressor Protein p53 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

4233

Références

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Auteurs

Yu Lei (Y)

Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Shantou University Medical College, Shantou, 515041, Guangdong, China.
Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Jinjiang Hospital for Maternal and Child Health Care, 66 Jingxiu Road, Chengdu, 610066, China.

Shuling Zhou (S)

Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Shantou University Medical College, Shantou, 515041, Guangdong, China.
Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Jinjiang Hospital for Maternal and Child Health Care, 66 Jingxiu Road, Chengdu, 610066, China.

Qiaoling Hu (Q)

Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Shantou University Medical College, Shantou, 515041, Guangdong, China.

Xueling Chen (X)

Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Shantou University Medical College, Shantou, 515041, Guangdong, China.

Jiang Gu (J)

Department of Pathology and Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Shantou University Medical College, Shantou, 515041, Guangdong, China. 2523381625@qq.com.
Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu Jinjiang Hospital for Maternal and Child Health Care, 66 Jingxiu Road, Chengdu, 610066, China. 2523381625@qq.com.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Facteurs de transcription à motifs basiques hélice-boucle-hélice et à glissière à leucines › Carbohydrate response element binding protein...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Carbohydrate response element binding protein...
questionsmedicales.fr › Métabolisme › Métabolisme glucidique › Carbohydrate response element binding protein...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Cycle cellulaire › Points de contrôle du cycle cellulaire › Carbohydrate response element binding protein...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Carbohydrate response element binding protein...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Tumeurs de l'intestin › Tumeurs du côlon › Carbohydrate response element binding protein...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Carbohydrate response element binding protein...
questionsmedicales.fr › Phénomènes physiologiques › Constitution physique › Prédisposition aux maladies › Carbohydrate response element binding protein...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Carbohydrate response element binding protein...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Glycolyse › Carbohydrate response element binding protein...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Carbohydrate response element binding protein...
questionsmedicales.fr › Métabolisme › Métabolisme lipidique › Lipogenèse › Carbohydrate response element binding protein...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Carbohydrate response element binding protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › Carbohydrate response element binding protein...