Signal transduction disturbance related to hepatocarcinogenesis in mouse by prolonged exposure to Nanjing drinking water

Abstract

Toxicogenomic approaches were used to investigate the potential hepatocarcinogenic effects on mice by oral exposure to Nanjing drinking water (NJDW). Changes in the hepatic transcriptome of 3 weeks male mice (Mus musculus) were monitored and dissected after oral exposure to NJDW for 90 days. No preneoplastic and neoplastic lesions were observed in the hepatic tissue by the end of NJDW exposure. However, total of 746 genes were changed transcriptionally. Thirty-one percent of differentially expressed genes (DEGs) were associated with the functional categories of cell cycle regulation, adhesion, growth, apoptosis, and signal transduction, which are closely implicated in tumorigenesis and progression. Interrogation of Kyoto Encyclopedia of Genes and Genomes revealed that 43 DEGs were mapped to several crucial signaling pathways implicated in the pathogenesis of hepatocellular carcinoma (HCC). In signal transduction network constructed via Genes2Networks software, Egfr, Akt1, Atf2, Ctnnb1, Hras, Mapk1, Smad2, and Ccnd1 were hubs. Direct gene-disease relationships obtained from Comparative Toxicogenomics Database and scientific literatures revealed that the hubs have direct mechanism or biomarker relationships with hepatocellular preneoplastic lesions or hepatocarcinogenesis. Therefore, prolonged intake of NJDW without employing any indoor water treatment strategy might predispose mouse to HCC. Furthermore, Egfr, Akt1, Ctnnb1, Hras, Mapk1, Smad2, and Ccnd1 were identified as promising biomarkers of the potential combined hepatocarcinogenicity.

Network Pharmacology-Based Exploration on the Intervention of Qinghao Biejia Decoction on the Inflammation-Carcinoma Transformation Process of Chronic Liver Disease via MAPK and PI3k/AKT Pathway

“…MAPK1 (Mitogen-activated protein kinase 1) also known as ERK2(Extracellular signal-regulated kinase 2), is a member of the MAPK family and the core signal transductor of the MAPK/ERK pathway [47], whose cascade is controlled by RAF, MEK1/2 and ERK1/2 protein. MAPK signaling pathway is a process of cascade phosphorylation, the core members of which include: MAP kinase kinase kinase (MAPKKK), MAP kinase kinase (MAPKK) and MAP kinase (MAPK).…”