Differentially expressed genes analysis and target genes prediction of miR-22 in breast cancer

Objective miR-22 is highly active in breast cancer, especially in the luminal B and HER2 subtypes.However, the detailed potential of the use of target genes for miR-22 in breast cancer are still unclear. Inthis study, we aimed to discover potential genes and the miRNA-DEGs network of miR-22 in breast cancerusing bioinformatics approaches.Methods Analysis of microarray data GSE17508 (including 3 miR-22 knockout samples and 3 controls)obtained from the Gene Expression Omnibus (GEO) database was performed. Differentially expressedgenes (DEGs) between the miR-22 knockout samples and the three control samples were detected usingGEO2R. The gene ontology (GO) functional enrichment analysis and protein-protein interaction (PPI)network of DEGs were performed using the online tool Metascape and STRING database, separately. ThemiR-22 and DEG networks were obtained from the miRNet database. Cytoscape software was used toconstruct and analyze a merged miRNA-DEG network. The online tools database, mirDIP 4.1, was used topredict miR-22 target genes.Results Certain DEGs and miRNAs may be potential targets for predicting and treating miR-22 expressedbreast cancer.Conclusion We constructed a prognostic model of rectal adenocarcinomas based on four immunerelatedlncRNAs by analyzing the data based on TCGA database, with high prediction accuracy. We alsoidentified two biomarkers with poor prognosis (PXN-AS1 and AL158152.2) and one biomarker with goodprognosis (LINC01871).

Relationship between miR-7-5p expression and ^(125)I seed implantation efficacy in pancreatic cancer and functional analysis of target genes

Objective The aim of this study was to investigate the relationship between miR-7-5p expression and intertissue-^(125)I irradiation sensitivity in pancreatic cancer tissues and to analyze the function of target genes.Methods Thirty-seven patients with unresectable pancreatic ductal adenocarcinoma(PDAC)treated with radioactive ^(125)I seed implantation were enrolled.RT-PCR was used to detect the expression level of miR-7-5p in cancer tissues and analyze the relationship between miR-7-5p expression and ^(125)I radiation sensitivity.Bioinformatic software and online tools were used to predict the miR-7-5p target genes and analyze their functional annotation and pathway enrichment.Results Radioactive ^(125)I seed implantation was followed up for 2 months.The objective response rate of the miR-7-5p high expression group was 65.0%(13/20),whereas the objective response rate of the miR-7-5p low expression group was 5.88%(1/17),and the difference between the two groups was statistically significant(χ^(2)=13.654,P<0.001).A total of 187 target genes were predicted using three databases.GO functional annotation showed that target genes were mainly involved in cellular response to insulin stimulus,regulation of gene expression by genetic imprinting,cytosol,peptidyl-serine phosphorylation,bHLH transcription factor binding,cargo loading into vesicles,cellular response to epinephrine stimulus,and nucleoplasm.KEGG pathway enrichment analysis showed that target genes were mainly involved in the ErbB signaling pathway,HIF-1 signaling pathway,axon guidance,longevity regulatory pathway,endocrine resistance,glioma,choline metabolism in cancer,and EGFR tyrosine kinase inhibitor drug resistance.Molecular complex detection analysis by Cytoscape revealed that PIGH,RAF1,EGFR,NXT2,PIK3CD,PIK3R3,ERBB4,TRMT13,and C5orf22 were the key modules of miR-7-5p target gene clustering.Conclusion The expression of miR-7-5p in pancreatic cancer tissues positively correlated with the radiosensitivity of ^(125)I seeds.Via targeted gene regulation,miR-7-5p acts on the network of multiple signaling pathways in PDAC and participates in its occurrence and development.Thus,miR-7-5p may become a predictive index of ^(125)I seed implantation therapy sensitivity in PDAC patients.

Differential gene screening and functional analysis in docetaxel-resistant prostate cancer cell lines

Objective Docetaxel-based combination chemotherapy has traditionally been the standard treatment for metastatic castration-resistant prostate cancer(PCa).However,most patients eventually develop resistance to this treatment,which further reduces their survival.This study aimed to determine key molecular genes in docetaxel-resistant PCa cell lines using bioinformatic approaches.Methods The analysis of microarray data GSE33455(including DU-145/DU-145R and PC-3/PC-3R cell lines)obtained from the Gene Expression Omnibus(GEO)database was performed using GEO2R.Differentially expressed genes(DEGs)of DU-145/DU-145R and PC-3/PC-3R cell lines were selected,and the intersection of DEGs between the two groups was obtained.DEGs were annotated with the Gene Ontology(GO)function and enriched with the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway using an online platform(https://cloud.oebiotech.cn/task/detail/array_enrichment/).The online tool Search Tool for the Retrieval of Interacting Genes(https://string-db.org/)was used to obtain the DEG network graph and matrix list,which was imported into Cytoscape 3.6.1 and analyzed using the Molecular Complex Detection plug-in to detect potential functional modules in the network.Results A total of 131 intersection DEGs were identified between non-treated and docetaxel-resistant PCa cell lines.GO functional annotation showed that the main genes involved were present in the plasma membrane and were involved in positive regulation of ubiquitin-protein transferase activity,positive regulation of pseudopodium assembly,centriolar subdistal appendage,and heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules.KEGG pathway enrichment analysis revealed that DEGs were mainly involved in IL-17 signaling pathway,cytokine-cytokine receptor interaction,rheumatoid arthritis,legionellosis,and folate biosynthesis.We identified two distinct hubs of DEGs:(1)CD274,C-X-C motif chemokine ligand(CXCL)1,DExD/H-box helicase 58,CXCL2,CXCL8,colony-stimulating factor 2,C-X-C motif chemokine receptor 4(CXCR4),CXCL5,and CXCL6 and(2)argininosuccinate lyase,argininosuccinate synthase 1,and asparagine synthetase.Except for the CXCR4 gene that was downregulated,the other 11 genes showed upregulated expression.Conclusion Certain differential genes may be potential targets for predicting and treating metastatic docetaxel-resistant PCa.

Ethylene and salicylic acid synergistically accelerate leaf senescence in Arabidopsis

The phytohormones ethylene and salicylic acid(SA) have long been known to promote senescence, but their interplay during this process remains elusive. Here we report the synergistic effects of ethylene and SA on promoting leaf senescence in Arabidopsis. EIN3, a key transcription factor of ethylene signaling, physically interacted with the core SA signaling regulator NPR1 in senescing leaves. EIN3 and NPR1 synergistically promoted the expression of the senescence-associated genes ORE1 and SAG29.The senescence phenotype was more delayed for the ein3 eil1 npr1 triple mutant than ein3 eil1 or npr1 with ethylene or/and SA treatment. NPR1-promoted leaf senescence may depend on functional EIN3/EIL1.