Tryptase TPSD1 And Glycosylase UNG Computational Network Comparison For Systemic Regulating HCC

In this paper,tryptase delta 1(TPSD1)and uracil DNA glycosylase(UNG)are highly expressed in HCC compared with hepatitis/fibrosis(HBV or HCV infection)from GSE10140-10141.High UNG and TPSD1 feedback/up/downstream activation and inhibition molecular knowledge networks were constructed in HCC(HBV or HCV infection)by integrating SAM,Pearson,GRNInfer and DAVID,respectively.TPSD1 mitosis and neuroendocrine inhibition,and inflammatory response activation mechanisms are horizontally proposed and verified through the corresponding computational relative common knowledges containing one same molecule and molecular subnetworks,in comparison with UNG mitosis activation,innate immune and inflammatory response inhibition.TPSD1 mitosis inhibition but UNG activation,TPSD1 neuroendocrine and UNG innate immune response inhibition,TPSD1 inflammatory response activation but UNG inhibition are vertically proposed and verified through the corresponding interactive knowledges with different molecules and common subnetworks.TPSD1 and UNG mitosis,neuroendocrine and innate immune,and inflammatory response are negatively verified through proposing the same knowledge mechanisms but different streams and common subnetworks,respectively.1.TPSD1 mitosis inhibition but UNG activation mechanisms in HCCTPSD1 feedback-inhibitive BUB IB and CDC2 of mitotic nuclear division is proposed and verified horizontally through positive regulation of gene expression |G2/M transition of mitotic cell cycle | DNA replication,and vertically through transcription factor activity sequence specific DNA binding | cell cycle G1 to S control reactome common in BUB 1B,CDC2,E2F1,LAPTM4B,MCM4,MYBL2,NCAPH subnetworks.To negatively verify TPSD1 feedback-inhibitive mitotic nuclear division,TPSD1 feedback-interactive transcription factor activity sequence specific DNA binding is proposed to induce response to DNA damage stimulus | positive chemotaxis | nucleosome assembly in common DDX10,GML,HMGB2,PRSS1,SORT1,TNFRSF9,TP53I11 subnetworks,compared that TPSD1 feedback-inhibitive transcription factor activity sequence specific DNA binding induces cell cycle pathway in common BUB1B,CDC2,CDKN3,E2F1,LAPTM4B,MCM4,MYBL2,NCAPH subnetworks.TPSD1 upstream-inhibited BIRC5 and CCNA2 of mitotic nuclear division horizontally through ubiquitin protein transferase activity | zinc ion binding,and vertically through structural constituent of cytoskeleton| cell proliferation common in ACTG2,CCNA2,ESM1,TUBG1,UBE2C subnetworks.To negatively verify TPSD1 upstream-inhibited mitotic nuclear division,TPSD1 upstream-activated cell proliferation is proposed from Fc epsilon RI signaling pathway | carbohydrate binding in common CHRNA4,GDPD5,KCTD2,KLRC3,MAP2K6,MS4A2,NFKBIB,REG3A subnetworks,compared that TPSD1 upstream-inhibited cell proliferation results from embryonic stem cell in common ACTG2,CCNA2,ESM1,GPSM2,TUBG1,UBE2C subnetworks.UNG feedback-interactive CCNB1 and TUBG1 of M phase horizontally through cellular response to hypoxia | G2/M checkpoint |protein complex assembly | p53 signaling pathway | structural constituent of cytoskeleton,and vertically through prostate and small cell lung cancer| transcription factor activity sequence specific DNA binding | DNA replication initiation | viral carcinogenesis | chromatin common in ACTG2,BIRC5,CCNB1,E2F1,MCM4 subnetworks.To negatively verify UNG feedback-interactive M phase,UNG upstream-activated positive regulation of transcription DNA templated is proposed to induce mitotic nuclear division | liver development in common UBE2C subnetwork,compared that UNG feedback-interactive transcription factor activity sequence specific DNA binding induces positive regulation of fibroblast proliferation | intrinsic apoptotic signaling pathway in response to DNA damage in common ACTG2,BIRC5,CCNB1,E2F1,LOX,MCM4 subnetworks.UNG upstream-activated NCAPH and NUSAP1 of mitotic chromosome condensation horizontally through microtubule binding |poly(A)RNA binding,and vertically through protein heterodimerization activity,cellular protein metabolic process | cellular response to DNA damage stimulus | translesion synthesis common in GPSM2,HIST1H3H,NCAPH,RFC4 subnetworks.To negatively verify UNG upstream-activated mitotic chromosome condensation,UNG feedback-interactive protein heterodimerization activity is proposed to induce protein ubiquitination and sumoylation | negative regulation of apoptosis in common BIRC5,E2F1 subnetworks,compared that UNG upstream-activated protein heterodimerization activity induces positive regulation of apoptotic process | cellular response to DNA damage stimulus |enzyme binding in common GPSM2,RFC4 subnetworks.2.TPSD1 neuroendocrine and UNG innate immune response inhibition mechanisms in HCCTPSD1 feedback-inhibitive CDKN3 and SPINK 1 of endocrine and CNS horizontally through no direct relative knowlegde,and vertically through positive regulation of gene expression | transcription factor activity sequence specific DNA binding | cell cycle G1 to S control reactome common in CDC2,CDKN3,E2F1,LAPTM4B,MCM4 subnetworks.To negatively verify TPSD1 feedback-inhibitive endocrine and CNS,TPSD1 downstream-activating endocrine and CNS is proposed from cell cell signaling in common FGF9,FOLR1,NINJ2,STX1A,TBL3,TSHB subnetworks.UNG feedback-inhibitive LGALS3 and NFKBIB of innate immune response horizontally through extracellular matrix organization |influenza A,and vertically through cognition | synaptic transmission |neurogenesis | small molecule metabolic process common in CHL1,CHRNA4,FOLR1,PRSS1,TPST2 subnetworks.To negatively verify UNG feedback-inhibitive innate immune response,UNG upstream-inhibited synaptic transmission is proposed fr-om potassium ion transport| signal transduction in common ARHGDIG,EIF1AX,SSTR5 subnetworks,compared that UNG feedback-inhibitive synaptic transmission results from regulation of membrane potential | secretory pathway in common CHL1,CHRNA4,FOLR1,KIAA0513,PRSS1,RIMS3,TPST2 subnetworks.UNG downstream-inhibiting HMGB2 and MS4A2 of innate immune response horizontally through response to endogenous stimulus| protein domain specific binding | response to lipopolysaccharide |inflammatory response,and vertically through synaptic transmission common in HMGB2,RNF185,TNFRSF9 subnetworks.To negatively verify UNG downstream-inhibiting innate immune response,UNG feedback-inhibitive synaptic transmission is proposed from neuroactive ligand receptor interaction | secretory pathway in common CHL1,CHRNA4,FOLR1,KIAA0513,PRSS1,RIMS3,TPST2 subnetworks,compared that UNG downstream-inhibiting synaptic transmission results from protein domain specific binding in common HMGB2,MS4A2,RNF185,TNFRSF9 subnetworks.3.TPSD1 inflammatory response activation but UNG inhibition mechanisms in HCCTPSD1 feedback-interactive CHST1 and TNFRSF9 of inflammatory response horizontally through multicellular organismal development | response to lipopolysaccharide,and vertically through serine type endopeptidase activity | axon guidance | identical protein binding | protein autophosphorylation | pancreatic secretion | blood coagulation common in CHST1,EPHA4,ISG20,LGALS3,PRSS1 subnetworks.To negatively verify TPSD1 feedback-interactive inflammatory response,TPSD1 downstream-inhibiting protein autophosphorylation is proposed to induce zinc ion binding | liver development | M phase of mitotic cell cycle in common FOXM1,HIST1H2BJ,STMN1 subnetworks,compared that TPSD1 feedback-interactive protein autophosphorylation induces axon guidance | blood coagulation | calcium signaling pathway in common CHL1,CHST1,EPHA4,PRSS1 subnetworks.TPSD1 upstream-activated MS4A2 and REG3A of inflammatory response horizontally through Fc epsilon RI | carbohydrate binding,and vertically through toll like receptor signaling | cholinergic synapse common in CHRNA4,KLRC3,MAP2K6,NFKBIB,REG3A subnetworks.To negatively verify TPSD1 upstream-activated inflammatory response,TPSD1 feedback-interactive glutamatergic synapse is proposed from transmission of nerve impulse | protein kinase activity in common CHST1,PRSS1,SSTR5 subnetworks,compared that TPSD1 upstream-activated cholinergic synapse results from potassium and voltage gated ion channel activity in common AMELY,KCNQ3,KLRC3,MAP2K6,REG3A,RNF185,SYN2,TPST2 subnetworks.UNG downstream-inhibiting MS4A2 and TNFRSF9 of inflammatory response horizontally through innate immune response |negative regulation of cell proliferation,and vertically through neurotransmitter secretion | protein domain specific binding common in HMGB2,RNF185,TNFRSF9 subnetworks.To negatively verify UNG downstream-inhibiting inflammatory response,UNG downstream-activating axon guidance is proposed from zinc ion binding in common CCNB2,DLG7,ESM1,IGF2BP3,MMP9 subnetworks,compared that UNG downstream-inhibiting neurotransmitter secretion results from protein domain specific binding in common HMGB2,MS4A2,RNF1 85,TNFRSF9 subnetworks.Firstly comprehensive and systematical large data calculation of tryptase TPSD1 mitosis and neuroendocrine inhibition,and inflammatory response activation mechanisms fill the gap in the current study field and lay the foundations for the diagnosis and treatment of early-stage HCC.Glycosylase UNG mitosis activation,innate immune and inflammatory response inhibition mechanisms expand theoretical and applied research,and have significant implications for the diagnosis and treatment of advanced HCC.The new systematic comparative study of TPSD1 mitosis inhibition but UNG activation,TPSD1 neuroendocrine and UNG innate immune response inhibition,TPSD1 inflammatory response activation but UNG inhibition provides the important theoretical basis and application values for the diagnosis and treatment of HCC.