Identification of miR-۲۱۸-۵p and TWIST۱TF as regulators of potential therapeutic genome targets(FN۱,CTNNB۱,GAPDH,ANXA۲,COL۱A۱,MMP۱۴,ITGAV,CFL۱,RUNX۲,CTTN,ACTN۱,TIMP۱) in pancreatic cancerby Bioinformatics Analysis

Introduction: Pancreatic cancer represents the fourth dominantreason for tumor‐relevant fatalities in developed states.The identification of novel gene targets is critical to improvingcurrent therapeutic methods. This research is aimed at selectinghub genes that can act as candidate therapeutic target genes inPC.Methods: Gene expression profiles of datasets GSE۱۸۶۸۳۵were extracted from the GEO database. GO analysis and KEGGanalysis were conducted to identify the functional correlation ofthe DEGs. STRING and Cytoscape were used to establish theprotein-protein-interaction network. Cytoscape with the filterof degree, betweenness-centrality, and closeness-centrality wasperformed to identify hub genes. Using Oncodb survival analysisbased on hub gene expression was performed with clinicalinformation from the TCGA database. GEPIA was employed tovalidate the results by RNA-seq expression data. The upstreamtranscription-factor, GO analysis, and potential mechanism ofselected genes and their interacting proteins were all investigatedusing Enrichr.Results: ۶۳۵ DEGs were identified. ۲۱۵ upregulated genes withp-value<۰.۰۵ and logFC>۱ selected. According to SRING andCytoscape PPI analysis FN۱,CTNNB۱,GAPDH,ANXA۲,COL۱A۱,MMP۱۴, ITGAV, CFL۱, RUNX۲,CTTN,ACTN۱,TIMP۱has the most degree, betweenness-centrality, and closenesscentralityinteractions in nodes. GO terms and Reactome۲۰۲۲pathway analysis results revealed enrichment in tumor-associatedpathways, including the extracellular-matrix-organization.According to MSigDB, these genes were engaged in epithelialmesenchymaltransition and angiogenesis. GEPIA analysis revealeda correlation between high expression of these genes andlower survival chances in Pancreatic-adenocarcinoma patients.Additional enrichment analysis using Enrichr revealed thatTWIST۱ is an upstream TF that can regulate the expression ofthese proteins. Finally, using miRTarbase database we discoveredthat hsa- miR-۲۱۸-۵p can regulate the expression of thesegenes.Conclusion: We discovered that FN۱, CTNNB۱, GAPDH,ANXA۲, COL۱A۱, MMP۱۴, ITGAV,CFL۱,RUNX۲,CTTN,ACTN۱,TIMP۱ significantly correlated with poor prognosis.We predicted that the TWIST۱ TF might be involved inregulating FN۱,CTNNB۱,GAPDH,ANXA۲,COL۱A۱,MMP۱۴,ITGAV,CFL۱,RUNX۲, CTTN, ACTN۱,TIMP۱. We are suggestingthat TWIST۱ as a proto-oncogene can be downregulatedin pancreatic cancer. Thus, treatment strategies that targettargeted gene expression, by hsa-miR-۲۱۸-۵p may inhibit epithelial-mesenchymal-transition and angiogenesis of pancreaticcancer cells.