HNF4α is possibly the missing link between epithelial-mesenchymal transition and Warburg effect during hepatocarcinogenesis.
Mice
Animals
Humans
Carcinoma, Hepatocellular
/ pathology
Liver Neoplasms
/ pathology
Epithelial-Mesenchymal Transition
/ genetics
Mice, Nude
Cell Line, Tumor
Neoplasm Recurrence, Local
/ genetics
Hepatocyte Nuclear Factor 4
/ genetics
Gene Expression Regulation, Neoplastic
Cell Proliferation
/ genetics
HNF4α overexpression
Warburg effect
aerobic glycolysis
epithelial-mesenchymal transition
hepatocellular carcinoma
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
revised:
27
11
2022
received:
22
09
2022
accepted:
02
12
2022
medline:
4
4
2023
pubmed:
9
12
2022
entrez:
8
12
2022
Statut:
ppublish
Résumé
Hepatocellular carcinoma (HCC) is a heterogeneous, late-diagnosed, and highly recurrent malignancy that often affects the whole body's metabolism. Finding certain theranostic molecules that can address current concerns simultaneously is one of the priorities in HCC management. In this study, performing protein-protein interaction network analysis proposed hepatocyte nuclear factor 4 alpha (HNF4α) as a hub protein, associating epithelial-mesenchymal transition (EMT) to reprogrammed cancer metabolism, formerly known as the Warburg effect. Both phenomena improved the compensation of cancerous cells in competitive conditions. Mounting evidence has demonstrated that HNF4α is commonly downregulated and serves as a tumor suppressor in the HCC. Enhancing the HNF4α mRNA translation through a specific synthetic antisense long non-coding RNA, profoundly affects both EMT and onco-metabolic modules in HCC cells. HNF4α overexpression decreased featured mesenchymal transcription factors and improved hepatocytic function, decelerated glycolysis, accelerated gluconeogenesis, and improved dysregulated cholesterol metabolism. Moreover, HNF4α overexpression inhibited the migration, invasion, and proliferation of HCC cells and decreased metastasis rate and tumor growth in xenografted nude mice. Our findings suggest a central regulatory role for HNF4α through its broad access to a wide variety of gene promoters involved in EMT and the Warburg effect in human hepatocytes. This essential impact indicates that HNF4α may be a potential target for HCC treatment.
Identifiants
pubmed: 36479791
doi: 10.1111/cas.15686
pmc: PMC10067433
doi:
Substances chimiques
Hepatocyte Nuclear Factor 4
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1337-1352Informations de copyright
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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