Identifying miltefosine-resistant key genes in protein–protein interactions network and experimental verification in Iranian Leishmania major

2019 ◽  
Vol 46 (5) ◽  
pp. 5371-5388 ◽  
Author(s):  
Niloofar Lari ◽  
Razieh Jalal ◽  
Zarrin Minuchehr ◽  
Majid Rajabian Noghondar
Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Xue Wu ◽  
Yuan Li ◽  
Baoan Chen

Background:Mantle cell lymphoma (MCL) is the secondary common B cell lymphoma subtype that comprises 6 to 8% of non-Hodgkin's lymphoma, and is closely related to the poor clinical outcomes. Previous studies have focussed on the mechanisms mediating ibrutinib resistance, the first-in-class oral covalent inhibitor of Bruton's tyrosine kinase (BTK). The aims of the this study is to identify key genes related to the FGFR1 Knockdown in Mantle cell lymphoma cell line (Z-138) that has been proved to play a vital role in MCL progression. Methods:GSE138127 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between vector control and the Knockdown of FGFR1 charactered by ibrutinib resistance. The GO and GSEA were carried out by WEB-based GEne SeT AnaLysis Toolkit (WebGestalt) to do the functional enrichment analysis. The network analysis of protein-protein interactions (PPIs), TF-gene interaction were carried out by Network Analyst 3.0 to identify hub genes. And the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Results:In total, 175 DEGs were obtained, of which 87 and 88 were up- and down-regulated, respectively. Three hub genes (CDK1, CCND1) were identified and associated to cell cycle and DNA replication. FOXC1 were identified as the potential Transcription factors in the biological process. Conclusion:CDK1, CCND1 may affect the cell cycle regulated by FOXC1, and represent the new candidate molecular markers of the occurrence of ibrutinib resistance. Keywords: Mantle cell lymphoma (MCL), ibrutinib resistance, Network Analyst, Microarray, Protein-protein interactions, Molecular markers Disclosures No relevant conflicts of interest to declare.


2011 ◽  
Vol 20 (6) ◽  
pp. 1060-1068 ◽  
Author(s):  
Michael A. Gorman ◽  
Alex D. Uboldi ◽  
Peter J. Walsh ◽  
Kher Shing Tan ◽  
Guido Hansen ◽  
...  

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 403-412
Author(s):  
Chao Han ◽  
Lei Jin ◽  
Xuemei Ma ◽  
Qin Hao ◽  
Huajun Lin ◽  
...  

AbstractBackgroundThis study identified key genes in gastric cancer (GC) based on the mRNA microarray GSE19826 from the Gene Expression Omnibus (GEO) database and preliminarily explored the relationships among the key genes.MethodsDifferentially expressed genes (DEGs) were obtained using the GEO2R tool. The functions and pathway enrichment of the DEGs were analyzed using the Enrichr database. Protein–protein interactions (PPIs) were established by STRING. A lentiviral vector was constructed to silence RUNX2 expression in MGC-803 cells. The expression levels of RUNX2 and FN1 were measured. The influences of RUNX2 and FN1 on overall survival (OS) were determined using the Kaplan–Meier plotter online tool.ResultsIn total, 69 upregulated and 65 downregulated genes were identified. Based on the PPI network of the DEGs, 20 genes were considered hub genes. RUNX2 silencing significantly downregulated the FN1 expression in MGC-803 cells. High expression of RUNX2 and low expression of FN1 were associated with long survival time in diffuse, poorly differentiated, and lymph node-positive GC.ConclusionHigh RUNX2 and FN1 expression were associated with poor OS in patients with GC. RUNX2 can negatively regulate the secretion of FN1, and both genes may serve as promising targets for GC treatment.


2011 ◽  
Vol 49 (08) ◽  
Author(s):  
LC König ◽  
M Meinhard ◽  
C Sandig ◽  
MH Bender ◽  
A Lovas ◽  
...  

1974 ◽  
Vol 31 (03) ◽  
pp. 403-414 ◽  
Author(s):  
Terence Cartwright

SummaryA method is described for the extraction with buffers of near physiological pH of a plasminogen activator from porcine salivary glands. Substantial purification of the activator was achieved although this was to some extent complicated by concomitant extraction of nucleic acid from the glands. Preliminary characterization experiments using specific inhibitors suggested that the activator functioned by a similar mechanism to that proposed for urokinase, but with some important kinetic differences in two-stage assay systems. The lack of reactivity of the pig gland enzyme in these systems might be related to the tendency to protein-protein interactions observed with this material.


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