CUL4B, NEDD4, and UGT1AS involve in the TGF-β signalling in hepatocellular carcinoma



Título del documento: CUL4B, NEDD4, and UGT1AS involve in the TGF-β signalling in hepatocellular carcinoma
Revista: Annals of hepatology
Base de datos: PERIÓDICA
Número de sistema: 000407481
ISSN: 1665-2681
Autors: 1
2
1
2
1
1
1
1
Institucions: 1Harbin Medical University, The Affiliated Tumor Hospital, Harbin, Heilongjiang. China
2Harbin Medical University, The Second Affiliated Hospital, Harbin, Heilongjiang. China
Any:
Període: Jul-Ago
Volum: 15
Número: 4
Paginació: 568-576
País: México
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Analítico, descriptivo
Resumen en inglés TGF β signalling is involved in pathogenesis and progress of hepatocellular carcinoma (HCC). This bioinformatics study consequently aims to determine the underlying molecular mechanism of TGF-β activation in HCC cells. Dataset GSE10393 was downloaded from Gene Expression Omnibus, including 2 Huh-7 (HCC cell line) samples treated by TGF-β (100 pmol/L, 48 h) and 2 untreated samples. Differentially expressed genes (DEGs) were screened using Limma package (false discovery rate < 0.05 and |log2 fold change| > 1.5), and then enrichment analyses of function, pathway, and disease were performed. In addition, protein-protein interaction (PPI) network was constructed based on the PPI data from multiple databases including INACT, MINT, BioGRID, UniProt, BIND, BindingDB, and SPIKE databases. Transcription factor (TF)-DEG pairs (Bonferroni adjusted p-value < 0.01) from ChEA database and DEG-DEG pairs were used to construct TF-DEG regulatory network. Furthermore, TF-pathway-DEG complex network was constructed by integrating DEG-DEG pairs, TF-DEG pairs, and DEG-pathway pairs. Results. Results. Results. Totally, 209 DEGs and 30 TFs were identified. The DEGs were significantly enriched in adhesion-related functions. PPI network indicted hub genes such as CUL4B and NEDD4. According to the TF-DEG regulatory network, the two hub genes were targeted by SMAD2, SMAD3, and HNF4A. Besides, the 11 pathways in TF-pathway-DEG network were mainly enriched by UGT1A family and CYP3A7, which were predicted to be regulated by SMAD2, SMAD3, SOX2, TP63, and HNF4A. Conclusions. TGF-β might influence biological processes of HCC cells via SMAD2/SMAD3-NEDD4, HNF4A-CUL4B/NEDD4, SOX2/TP63/HNF4A-CYP3A7, and SMAD2/SMAD3/SOX2/TP63/HNF4A-UGT1As regulatory pathways
Disciplines Medicina
Paraules clau: Gastroenterología,
Oncología,
Genética,
Carcinoma hepatocelular,
Factores de transcripción,
Genes,
Expresión diferencial
Keyword: Medicine,
Gastroenterology,
Oncology,
Genetics,
Hepatocellular carcinoma,
Transcription factors,
Genes,
Differential expression
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