RESUMO

UNLABELLED:  Introduction and Aim. TGF-ß signalling is involved in pathogenesis and progress of hepatocellular carcinoma (HCC). This bioinformatics study consequently aims to determine the underlying molecular mechanism of TGF- ß activation in HCC cells. MATERIAL AND METHODS: Dataset GSE10393 was downloaded from Gene Expression Omnibus, including 2 Huh-7 (HCC cell line) samples treated by TGF- ß (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: 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- ß 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.

Assuntos

Carcinoma Hepatocelular/genética , Proteínas Culina/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Glucuronosiltransferase/genética , Neoplasias Hepáticas/genética , Fator de Crescimento Transformador beta/metabolismo , Ubiquitina-Proteína Ligases/genética , Carcinoma Hepatocelular/metabolismo , Adesão Celular/genética , Linhagem Celular Tumoral , Proteínas Culina/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Bases de Dados Genéticas , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Perfilação da Expressão Gênica , Glucuronosiltransferase/metabolismo , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Ubiquitina-Proteína Ligases Nedd4 , Mapas de Interação de Proteínas , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Transdução de Sinais/genética , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo