PTHLH coupling upstream negative regulation of fatty acid biosynthesis and Wnt receptor signal to downstream peptidase activity-induced apoptosis network in human hepatocellular carcinoma by systems-theoretical analysis.

Studies were done on the analysis of biological processes in the same high expression (fold change ≥ 2) PTHLH-activated feedback negative regulation-mediated apoptosis gene ontology (GO) network of human hepatocellular carcinoma (HCC) compared with the corresponding low expression activated GO network of no-tumor hepatitis/cirrhotic tissues [hepatitis B virus (HBV) or hepatitis C virus (HCV) infection]. We proposed PTHLH-activated network that upstream included the regulation of apoptosis, signal transduction resulting in induction of apoptosis, signal transduction by p53 class mediator resulting in transcription of p21 class mediator, negative regulation of centriole replication, negative regulation of fatty acid biosynthesis, negative regulation of Wnt receptor signaling pathway, anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolism, apoptosis, induction of apoptosis, and negative regulation of phosphorylation. Downstream-network negative regulation of peptidase activity, anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolism, apoptosis, induction of apoptosis and negative regulation of phosphorylation, as a result of coupling upstream negative regulation of fatty acid biosynthesis and Wnt receptor signal to downstream peptidase activity-induced apoptosis in HCC. Our hypothesis was verified by the different PTHLH-activated feedback negative regulation-mediated apoptosis GO network of HCC compared with the corresponding inhibited GO network of no-tumor hepatitis/cirrhotic tissues, or the same compared with the corresponding inhibited GO network of HCC. PTHLH coupling upstream negative regulation of fatty acid biosynthesis and Wnt receptor signal to downstream peptidase activity-induced apoptosis network was constructed that upstream BRCA1, DKK1, BUB1B activated PTHLH, and downstream PTHLH-activated CST6, BUB1B, NTN1, PHLDA2 in HCC from GEO data set using gene regulatory network inference method and our programing.