In Silico analysis on the identification of has-mir-4271 associated with IGFBP4 gene in gastric cancer
In Silico analysis on the identification of has-mir-4271 associated with IGFBP4 gene in gastric cancer
Zahra Ahmadzadeh Chaleshtori,1Mehdi Roshanian bakhsh,2Pegah Javid,3Mansoureh Azadeh,4,*
1. Department of Biochemistry, Falavarjan Branch , Islamic Azad University, Isfahan,Iran 2. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran. 3. Zist Fanavari Novin Biotechnology Department, State Technical and Vocational Training Organization, Isfahan, Iran. 4. Zist Fanavari Novin Biotechnology Department, State Technical and Vocational Training Organization, Isfahan, Iran.
Introduction: Despite its high prevalence and mortality rate, gastric cancer (GC) can be prevented and detected globally, thanks to its genetic susceptibility. Helicobacter pylori infection, age, high salt intake, and low fruit and vegetable consumption are all factors contributing to the condition. In the present study, hub genes were identified and molecular mechanisms were revealed in GC.
Methods: Gene expression profiles were analyzed using GSE54129 from the GEO datasets. Gene Expression Analysis using GEO2R tool revealed the Differentially Expressed Genes (DEGs). Adj. p-value < 0.01 and log2FC (fold change) >3 were considered as the cut-off criteria. By using the DAVID database, enrichment analysis was conducted on the DEGs and their pathways with overlapping functions were identified in the KEGG database. The protein-protein interaction network graph (PPI) was obtained using the STRING database to analyze the interactions between DEGs. MicroRNASNP-v3 database revealed the miRNAs (miRs) associated with the Insulin Like Growth Factor Binding Protein 4 (IGFBP4) gene as well as the underlying signaling pathways that contribute to GC growth. The miRWalk database was used for detecting the interaction between IGFBP4 gene and associated miRs.
Results: Based on the current research, 24 DEGs were identified. The KEGG and DAVID databases showed that IGFBP4 gene is a member of the insulin-like growth factor binding protein (IGFBP) family, which controls the bioavailability, activity, and distribution of insulin-like growth factor (IGF)1 and -2 through high-affinity IGFBP/IGF complexesIn addition to being in the same family of proteins as insulin, IGF plays a role in the regulation of growth and development. Consequently, IGFBP4 can inhibit cancer cell growth by reducing IGF1 activity. Furthter results showed that By interfering with RNA-induced silencing complexes and interfering with the 3' untranslated regions of target mRNAs, has-mir-4271 could exert a suppressive effect on the IGFBP4 gene's activity by acting as a regulator of gene expression.
Conclusion: These findings imply that IGFBP4 could be a potential target in gene therapy for gastric cancer. Blocking of IGFBP4 expression in GC cells represses the IGF1 activity and may provide a novel treatment approach.