RESUMO
Background: ARF family proteins are a kind of small GTPases, which are involved in regulating a variety of basic functions of cells. In recent years, the role and molecular regulatory mechanisms of ARFs in tumor progression have received increasing attention, and research reports on most of their family members are increasing. However, research on the clinical and pathological relevance of ARF5 in cancer, especially in hepatocellular carcinoma, still needs to be improved. Methods: RNA-seq data in the Cancer Genome Atlas (TCGA) and genome tissue expression (GTEx) databases were used to analyze the expression and pathological data of ARFs family in Pan-cancer. Kaplan-Meier and Cox regression were used for prognostic analysis of ARF5 and Pan-cancer. Combined with ImmuCellAI database and TIMER2 database, the relationship between ARF5 expression and immune cell tumor infiltration in hepatocellular carcinoma (HCC) was analyzed. WGCNA is used to construct the co-expression gene network related to ARF5 expression in HCC and screen important modules and central genes. GO and KEGG path enrichment analysis were carried out for the genes in the modules with clinical significance. GSEA analysis was performed to take into account the role of genes with small differences. Finally, ceRNA network analysis was used to explore the molecular mechanism of miRNAs and lncRNAs regulating ARF5 expression. Results: ARFs family (ARF1, ARF3, ARF4, ARF5, ARF6) are generally highly expressed in Pan-cancer. ARF5 is significantly highly expressed in 29 cancers, and the high expression of ARF5 in HCC patients is significantly negatively correlated with OS, DFI, PFI and DSS, which may lead to cancer deterioration by participating in tumor immune infiltration of HCC. Through WGCNA analysis, the expression of ARF5 in HCC may be involved in many cellular processes that consume a lot of energy, such as ribosome formation, RNA and protein synthesis and lipids, as well as COVID-19, nonalcoholic fatty liver, neurodegenerative diseases and other disease pathways. Conclusion: ARFs, especially ARF5, are overexpressed in many human tumors. This study shows for the first time that ARF5 is significantly correlated with the poor prognosis of HCC patients, which may play a role as an oncogene, suggesting that ARF5 has the potential as a biomarker for the diagnosis and treatment of HCC.
RESUMO
The molecular mechanism of network regulation in the occurrence and development of colorectal cancer (CRC) has been constantly improved. Here, we investigated the biological effects of TEAD4-MAD2L1 axis on proliferation and metastasis of human CRC cells. This study revealed that the expressions of MAD2L1 and TEAD4 in CRC tissues and CRC cell lines were significantly higher than those in adjacent epithelial tissues and normal intestinal epithelial cell line NCM460, and their expressions were significantly positively correlated; Moreover, inhibiting the expression of MAD2L1 or TEAD4 can inhibit the proliferation and migration of CRC cells and promote apoptosis. In addition, the promoter region of MAD2L1 gene has a TEAD4 binding site (motif sequence), and the transcription of MAD2L1 is positively regulated by TEAD4 protein; The inhibition of promotion/migration and promotion of apoptosis of CRC cells by silencing TEAD4 can be saved by the high expression of MAD2L1. In conclusion, our study suggests that the transcription and expression of MAD2L1 is regulated by TEAD4, which further promotes the proliferation and migration of CRC cells in vitro and in vivo, and inhibits apoptosis. MAD2L1 and TEAD4 are potential biomarkers for colorectal cancer.