| In this study, parathyroid hormone-like hormone (PTHLH) four single molecular networks, which are activated and inhibited networks in no-tumor hepatitis/cirrhotic tissues, activated and inhibited networks in human hepatocellular carcinoma (HBV or HCV infection)(HCC), were selected from225significant high expression (fold change≥2) molecules of HCC compared with low expression of no-tumor hepatitis/cirrhotic tissues in GEO database GSE10140-10141, respectively. Four single molecular networks were computed biological processes and occurrence numbers of gene ontology (GO) in no-tumor hepatitis/cirrhotic tissues and HCC for finding new biomarkers of diagnosis and therapy in hepatocellular carcinoma. Calculating the four networks on their respective upstream, downstream or feedback biological processes and comparing GO biological processes differences of the activation and inhibition groups molecular network, we proposed and constructed the specific functions and mechanisms new molecular networks by gene regulatory network inference method and our programming. Our hypothesis was verified within other biological processes or multi-occurrence numbers (≥2) of the corresponding network, between the corresponding up-and down-stream and feedback networks, respectively.This work was supported by the National Natural Science Foundation of China (NO.60871100).21academic papers including16SCI, cited more than82times, have been published on international academic journals. Such as:Integrative Biology, Cell Biochemistry and Biophysics, Immunologic Research, Journal of Cellular Biochemistry, Cellular Physiology and Biochemistry, Cell Proliferation, Journal of Molecular Neuroscience, Journal of inflammation, Tumor Biology, Cellular and Molecular Neurobiology, Cell Biochemistry and Function, Journal of Receptors and Signal Transduction.The same and different biological processes were computed by up-and down-stream and feedback integrative comparisons between activated and inhibited PTHLH GO network of no-tumor hepatitis/cirrhotic tissues and the corresponding GO network of HCC. We totally proposed and constructed26networks as follows:The same activated PTHLH GO network of no-tumor hepatitis/cirrhotic tissues by up-and down-stream and feedback integrative comparisons with the corresponding HCC: feedback mitosis and downstream DNA replication-induced slow increase of cell numbers network; coupling downstream adenylate cyclase to androgen receptor signal-induced cell-cell adhesion network; coupling feedback phosphoinositide to G-protein receptor signal-induced cell differentiation network; coupling downstream positive regulation of protein ubiquitination to postreplication repair-induced epithelial cell differentiation network; coupling downstream negative regulation of Wnt receptor signal and fatty acid biosynthesis-induced regulation of apoptosis network.The same activated PTHLH GO network of HCC by up-and down-stream and feedback integrative comparisons with the corresponding no-tumor hepatitis/cirrhotic tissues:feedback mitosis and DNA replication-induced fast increase of cell numbers network; upstream leukocyte migration mediated-androgen receptor signal-induced cell motility network; coupling downstream adenylate cyclase activating pathway to positive regulation of I-kappaB kinase/NF-kappaB-induced chemotaxis network; coupling feedback phosphoinositide to G-protein receptor signal-induced cell adhesion network; upstream DNA damage response mediated-positive regulation of protein ubiquitination coupling postreplication repair to transcription-induced positive regulation of survival gene product activity network; coupling upstream negative regulation of fatty acid biosynthesis and Wnt receptor signal to downstream peptidase activity-induced apoptosis network.The different activated PTHLH GO network of no-tumor hepatitis/cirrhotic tissues by up-and down-stream and feedback integrative comparisons with the corresponding HCC:coupling upstream positive regulation of EGFR signal to protein transport-induced cell aging network; coupling downstream microtubule depolymerization to intermediate filament cytoskeleton organization and biogenesis-induced exocytosis network.The different activated PTHLH GO network of HCC by up-and down-stream and feedback integrative comparisons with the corresponding no-tumor hepatitis/cirrhotic tissues:upstream drug response-mediated protein prenylation and secretion coupling TGFβ and cGMP to DNA metabolism-induced positive regulation of microtubule polymerization network; downstream neutrophil immunity-mediated MAPK, phospholipase A2, NF-kappaB activation coupling potassium ion transport to lipid metabolism to actin filament organization-induced regulation of angiogenesis network; coupling feedback microtubule cytoskeleton organization to nucleic acid metabolism-induced regulation of cell growth network; downstream positive regulation of natural killer, immunoglobulin, mast and T cell cytotoxicity-mediated Rho signal coupling calcium ion transport-induced positive regulation of apoptosis network; coupling upstream negative regulation of caspase and microtubule depolymerization and transcription-induced anti-apoptosis network.The different inhibited PTHLH GO network of no-tumor hepatitis/cirrhotic tissues by up-and down-stream and feedback integrative comparisons with the corresponding HCC:downstream leukocyte adhesion-mediated protein amino acid N-linked glycosylation coupling Notch and JAK-STAT cascade to iron-sulfur cluster assembly-induced aging network; downstream stress response-mediated regulation of insulin secretion to liquid surface tension-induced regulation of cell-cell adhesion network; coupling downstream negative regulation of cell adhesion, ubiquitin ligase activity during mitotic cell cycle and endothelial cell differentiation-induced anti-apoptosis network.The different inhibited PTHLH GO network of HCC by up-and down-stream and feedback integrative comparisons with the corresponding no-tumor hepatitis/cirrhotic tissues:upstream T cell-mediated cytokine, metabotropic glutamate receptor and NF-kappaB-inducing kinase signal coupling keratan sulfate and polysaccharide metabolism to intermediate filament cytoskeleton organization-induced cell maturation network; downstream insulin stimulus mediated-glucose import coupling T cell homeostasis to endocytosis-induced growth network; coupling feedback microtubule depolymerization to collagen fibril organization-induced cell-matrix adhesion network; coupling downstream positive regulation of EGFR, FGFR, MAPKKK, Notch, smoothened signal and I-kappaB kinase/NF-kappaB cascade to steroid biosynthesis-induced regulation of growth network; coupling downstream negative regulation of EGFR, lipoprotein lipase, MAPK, Ras signal and sister chromatid cohesion-induced induction of apoptosis network. |
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