BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely ...BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.展开更多
Objective: To investigate the molecular mechanisms of Yuye Decotion in the treatment of diabetic kidney disease using network pharmacology methods and molecular docking techniques. Methods: Obtain the transcriptome ge...Objective: To investigate the molecular mechanisms of Yuye Decotion in the treatment of diabetic kidney disease using network pharmacology methods and molecular docking techniques. Methods: Obtain the transcriptome gene expression of diabetic nephropathy through GEO database, and extract genes related to autophagy. Screen the active ingredients and corresponding targets of Yuye Decoction through the TCMSP database, and map the drug prediction targets and disease targets to obtain the autophagy-related Yuye treatment targets for diabetic nephropathy point. Use String database combined with Cytoscape 3.7.2 software to construct the "drug-active ingredient-target" network and protein interaction network of Yuyetang for the treatment of diabetic nephropathy. The target point of liquid soup in the treatment of diabetic nephropathy was analyzed by GO biological process enrichment analysis and KEGG pathway enrichment analysis, and finally used Pymol and other software to analyze the core active components of Yuye Decotion and The core target protein undergoes molecular docking verification. Results: (i)100 eligible diabetic nephropathy and autophagy related genes were screened, and the potential targets of Yuye Decoction were 1,428. The acquired genes related to diabetic nephropathy and autophagy were mapped to potential targets of Yuye Decoction, and 22 therapeutic targets were obtained. GO biological process enrichment analysis and KEGG pathway enrichment analysis found that the pathways related to autophagy in the treatment of diabetic nephropathy by Yuye Decoction may include mTOR signaling pathway, phospholipase D signaling pathway, insulin resistance, EGFR tyrosine kinase inhibitor resistance, Apoptosis, PI3K /Akt signaling pathway, NF-κB signaling pathway, etc. (ii)The protein interaction network shows that VEGFA, ERBB2, GASP3, MAPK8, MYC, CDKN1A, EGFR, BCL2L1 may be the key targets of Yuye Decoction in the treatment of diabetic nephropathy. Molecular docking realizes the binding of 4 core active ingredients to 8 core target proteins. Conclusions: The research results show that Yuye Decoction treats diabetic nephropathy through multi-component, multi-target, and multi-pathway action, and provides new theoretical basis for the study of pharmacological effects and clinical application of Yuye Decoction in the treatment of diabetic nephropathy in autophagy-related aspects.展开更多
Accumulation of aberrant proteins and inclusion bodies are hallmarks in most neurodegenerative diseases. Consequently, these aggregates within neurons lead to toxic effects, overproduction of reactive oxygen species a...Accumulation of aberrant proteins and inclusion bodies are hallmarks in most neurodegenerative diseases. Consequently, these aggregates within neurons lead to toxic effects, overproduction of reactive oxygen species and oxidative stress. Autophagy is a significant intracellular mechanism that removes damaged organelles and misfolded proteins in order to maintain cell homeostasis. Excessive or insufficient autophagic activity in neurons leads to altered homeostasis and influences their survival rate, causing neurodegeneration. The review article provides an update of the role of autophagic process in representative chronic and acute neurodegenerative disorders.展开更多
基金Supported by the National Natural Science Foundation of China,No.U1504815 and No.U1504808
文摘BACKGROUND Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1 A/1 B-light chain 3(LC3) and perineural invasion(PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.AIM To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.METHODS Two sets of gene expression profiles of pancreatic cancer/normal tissue(GSE16515 and GSE15471) were collected from the Gene Expression Omnibus.Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.RESULTS Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition,65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene,which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.CONCLUSION Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.
基金National Natural Science Foundation of China,Regional Fund(No.81860836)。
文摘Objective: To investigate the molecular mechanisms of Yuye Decotion in the treatment of diabetic kidney disease using network pharmacology methods and molecular docking techniques. Methods: Obtain the transcriptome gene expression of diabetic nephropathy through GEO database, and extract genes related to autophagy. Screen the active ingredients and corresponding targets of Yuye Decoction through the TCMSP database, and map the drug prediction targets and disease targets to obtain the autophagy-related Yuye treatment targets for diabetic nephropathy point. Use String database combined with Cytoscape 3.7.2 software to construct the "drug-active ingredient-target" network and protein interaction network of Yuyetang for the treatment of diabetic nephropathy. The target point of liquid soup in the treatment of diabetic nephropathy was analyzed by GO biological process enrichment analysis and KEGG pathway enrichment analysis, and finally used Pymol and other software to analyze the core active components of Yuye Decotion and The core target protein undergoes molecular docking verification. Results: (i)100 eligible diabetic nephropathy and autophagy related genes were screened, and the potential targets of Yuye Decoction were 1,428. The acquired genes related to diabetic nephropathy and autophagy were mapped to potential targets of Yuye Decoction, and 22 therapeutic targets were obtained. GO biological process enrichment analysis and KEGG pathway enrichment analysis found that the pathways related to autophagy in the treatment of diabetic nephropathy by Yuye Decoction may include mTOR signaling pathway, phospholipase D signaling pathway, insulin resistance, EGFR tyrosine kinase inhibitor resistance, Apoptosis, PI3K /Akt signaling pathway, NF-κB signaling pathway, etc. (ii)The protein interaction network shows that VEGFA, ERBB2, GASP3, MAPK8, MYC, CDKN1A, EGFR, BCL2L1 may be the key targets of Yuye Decoction in the treatment of diabetic nephropathy. Molecular docking realizes the binding of 4 core active ingredients to 8 core target proteins. Conclusions: The research results show that Yuye Decoction treats diabetic nephropathy through multi-component, multi-target, and multi-pathway action, and provides new theoretical basis for the study of pharmacological effects and clinical application of Yuye Decoction in the treatment of diabetic nephropathy in autophagy-related aspects.
文摘Accumulation of aberrant proteins and inclusion bodies are hallmarks in most neurodegenerative diseases. Consequently, these aggregates within neurons lead to toxic effects, overproduction of reactive oxygen species and oxidative stress. Autophagy is a significant intracellular mechanism that removes damaged organelles and misfolded proteins in order to maintain cell homeostasis. Excessive or insufficient autophagic activity in neurons leads to altered homeostasis and influences their survival rate, causing neurodegeneration. The review article provides an update of the role of autophagic process in representative chronic and acute neurodegenerative disorders.
