Co-expression network and function analysis of TP53 and NOTCH1 in head and neck squamous cell carcinoma / 局解手术学杂志

Objective To find out the expression relation between TP53 and NOTCH1,and to explore their effects in head and neck squamous cell carcinoma.Methods Obtained the differentially expressed genes data of head and neck squamous cell carcinoma from 279 samples in TCGA database.Analyzed the co-expression relation between TP53 and NOTCH1 through Pearson and Spearman method.Cbioportal was used to analyze their co-expressed genes.Establish the co-expression network of TP53 and NOTCH1 with String database.The pathway and function of co-expression network was identified through KEGG and DAVID database respectively.Results Among the 279 samples,TP53 and NOTCH1 was co-expressed in head and neck squamous cell carcinoma.(Pearson score =0.45;Spearman score =0.41) There were 182 interaction pairs of TP53 and NOTCH1 related co-expressed gene according to the String database.(Pearson and Spearman score ＞ 0.3)These genes were enriched in some pathways such as T cell receptor signaling pathway,cell cycle,cell adhesion molecules and so on.These genes were enriched in some tumor related function including immune response,regulation of transposition,regulation of apoptotic process,cell cycle,regulation of GTPase activity and so on.Conclusion TP53 and NOTCH1 was co-expressed.Through establishing co-expressed network of TP53 and NOTCH1 and bioinformatics analysis,their function and signaling pathway were explored.The data generated from this study could provide a new reference in mechanism research of head and neck squamous cell carcinoma.

FOXP3-related ceRNA network analysis in head and neck squamous cell carcinoma / 局解手术学杂志

Objective To explore the FOXP3-related mechanism underlying head and neck squamous cell carcinoma.Methods We used cbioportal to identify the co-expressed genes of FOXP3 in 279 samples from head and neck squamous cell carcinoma in TCGA database.We used String database to establish the co-expression network of FOXP3.The function of co-expression network was identified through DAVID database.We used miRTarBase and StarBase database to screen the microRNA,lncRNA and circRNA that regulate FOXP3.Finally,Cytoscape software was used to establish FOXP3-related ceRNA network.Results We found 950 FOXP3 related co-expressed gene.(Spearman score over 0.5) These genes were enriched in immune response including T cell,leukocyte and lymphocyte activation.CeRNA network revealed that 2 microRNAs (i.e.,miR-31-5p and miR-210-3p),42 lncRNAs (e.g.,XIST,TUG1,JRK and LINC00473) and 31 circRNAs (e.g.,ZNF223 _hsa_ circ_ 000898 and ISY1 _hsa _circ _001090) could regulate FOXP3.Conclusion We established FOXP3-related ceRNA network and identified 42 lncRNAs and 31 circRNAs that regulate FOXP3.The data generated from this study could provide a new cut point in research and treatment of head and neck squamous cell carcinoma.

Screening of functional gene modules and the potential anti-cancer drugs in hypopharyngeal cancer / 局解手术学杂志

Objective Screening the functional gene modules that can play important roles in hypopharyngeal cancer and the potential anti-cancer drugs.Methods GEO database and MeV software were employed to screen the differentially expressed genes in hypopharyngeal cancer.Using STRING database,the protein-protein interaction network was identified.MCODE plugin of Cytoscape was used to identify the functional gene modules in the network.Based on DAVID database,the functions of modules were identified.DrugBank was used to screen the potential drugs that regulate the target genes of modules.Results 1 222 differentially expressed genes including 219 interaction pairs were i-dentified in whole genome profiling(P <0.05 ).Seven functional modules were identified in the network.The results of function analysis showed the module genes were enriched in cancer development related-function ‘regulation of angiogenesis’,‘cell adhesion’,‘DNA meta-bolic process’.A total of 50 potential drugs that regulating the 5 modules were screened.Conclusion Five functional modules that regulate the progress of hypopharyngeal cancer were identified,and maybe they can promote hypopharyngeal cancer through some functions such as regulation of angiogenesis 18 up-regulated protein kinases were identified.Their kinase inhibitors may potential have a role in anti-cancer, which provides a new target point for molecular therapy of nasopharyngeal cancer.

The linkage between cell cycle S phase arrest and apoptosis on human hepatocellular carcinoma HepG2 induced by Na~+,K~+-ATPase inhibitors via regulating proteins associated with cell cycle / 中国药理学通报

Aim To investigate the effect of ouabain and cinobufogenin on cell proliferation,apoptosis and cell cycle on HepG2,and explore their molecular mechanism.Methods The anti-proliferative effect on HepG2 cells was determined by MTT assay.The HepG2 cells were stained with Hoechst 33342,and its morphological changes were observed under fluorescence microscope;The cell cycle was measured by flow cytometry.The Cyclin A1,CDK 2,PCNA and p21~(CIP1) expression levels of HepG2 cells treated with ouabain and cinobufogenin were dectected in mRNA and protein by Real time PCR and Western blot.Results Ouabain and cinobufogenin could inhibit cell proliferation on HepG2 cells,and the inhibitory effects were in time and dose dependent manners.The HepG2 cells treated with ouabain and cinobufogenin showed the typical morphological features of apoptosis.Cell cycle analysis showed that the S phase of HepG2 cells treated with ouabain and cinobufogenin increased significantly compared with the control group.Real-time quantitative PCR and Western blot results showed that ouabain and cinobufogenin could down-regulate Cyclin A1,CDK 2,and PCNA expressions(P<0.05)and up-regulate p21~(CIP1) expression(P<0.05).Conclusion Nα~+,K~+-ATPase inhibitor has the anti-proliferative effect on HepG2 cells and induce apoptosis and S phase arrest.These effects might be related with proteins associated with cell cycle closely.

Anti-tumor Mechanism of Artemisinin / 中国药房

OBJECTIVE:To detect the expression of genes of leukemia cell line K562 treated by artemisinin using the gene chip technology and to study the mechanism of artemisinin in the inhibition of leukemia cell line K562 on the molecular level. METHODS:K562 cells were treated with artemisinin for 24h,and then the morphological change of K562 cells were observed under invert microscope and fluorescence microscope. The cell cycle state was examined by flow cytometry analysis (FCM). Total RNA samples were extracted and reverse transcribed to cDNA. Cy3-labelled cDNA samples were hybridized with gene chips.The hybridization results were detected by Gene Pix 4100A. RESULTS: Under invert microscope,different degree of shrinkage of K562 cells was noted,karyoschisis was reduced,cell density was decreased and the numbers of drift cells were increased.Under fluorescence microscope,caryotin was highly concentrated,marginalized and agglomerated to relucent clump,i.e.apoptotic body. Flow cytometric analysis showed that ratio of cells in G2 phase increased markedly. Hybridization analysis showed down-regulation of cyclin D1,cdk4,cdk2,cdc2,DNA-PK,DNA-TopoI,mcl-1,erk,jnk and VEGF in the artemisinin-treated K562 cells.CONCLUSION: The mechanism for artemisinin to inhibit the proliferation of leukemia cell line K562 is related to its action to alter the gene expression of certain regulatory substances involved in cell cycle and induce apoptosis of leukemia cell line K562.

Up-expression of peroxisome proliferator-activated receptor-? and of retinoid X receptor-? enhances the inhibitory effect on tumor cells growth / 基础医学与临床

LOVO.PGZ significantly up-regulates the expression of PPAR? in MGC803 and LOVO cells,the expression of PPAR? was higher in combination group than PGZ alone(P

Human Tumor Cells Apoptosis Induced by Dihydroartemisinin and Its Molecular Mechanism / 中国药房

OBJECTIVE:To study the apoptosis of human leukemic cells induced by Dihydroartemisinin and its molecular mechanism.METHODS:Human leukemia K562 cells were treated by Dihydroartemisinin.The inhibitory effect on cell proliferation was assayed by MTT.Fluorescence microscopy was applied to observe the presence of apoptosis.The expression of caspase-3 was assayed with reverse transcription-polymerase chain reaction(RT-PCR).Levels of mitochondrial and cytoplasmic cytochrome C were determined using Western blot.RESULTS:After treatment with Dihydroartemisinin for 48 hours,the IC50 values of human leukemia K562 cells were 8? 10-5mol? L-1 detected at a wavelength of 570nm by MTT.Distinct morphology changes of cell apoptosis such as karyopyknosis and conglomeration were observed by Hoechst33342/PI staining.RT-PCR assay showed the expression of Caspase-3.Western-blot detection showed the decrease of mitochondrial cytochrome C concentration but the positive expression of cytoplasmic cytochrome C concentration.CONCLUSION:Dihydroartemisinin could inhibit proliferation and induce apoptosis of human leakemic K562 cells,this may partially attributed to the promotion of the delivery of cyt-c and the activation of caspase-3.

Studies on physical stress of soldiers undergone 100 kilometers march in battle gear / 解放军医学杂志

Objective To study the physical stress reactions of soldiers undergone 100 kilometer march in battle gear,and explore the mechanism of biochemical changes in special military physical training.Methods Thirty four soldiers of armed-police force,averagely aged 18.6?1.6 years,169.3?4.2cm in height,weighted 65.4?4.5kg and with one-year of military physical training experience,were involved in present study.The soldiers were loaded about 25 kilogram of battle gear in a supervised 100 kilometer march in three days.The changes on biochemical index after the march were analyzed.Results After 100 kilometer march in battle gear,significant decline were found in the following biochemistry indexes in the soldiers involved: HB(P