• Inhibition of the miR-3928-5p/INHBA interaction by rs1479520687 (G/A) disturb the regular Activin signaling pathway by changing the expression level of INHBA protein as a potential biomarker of GC
  • Alireza Mohebi,1 Mohammad Hossein Donyavi,2 Mohammad Rezaei,3 Mansoureh Azadeh,4,*
    1. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    2. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    3. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    4. Zist Fanavari Novin Biorechnology Institute, Isfahan, Iran


  • Introduction: One of the most prevalent diseases and a leading cause of cancer-related death is gastric cancer[1].Additionally, due to the significant tumor heterogeneity, the therapeutic response and prognosis vary at different stages. Therefore, it is highly desired to investigate the molecular mechanisms behind cancer invasion, metastasis, incidence, and prognosis from a genomics viewpoint, since this could lead to highly sensitive therapeutic modalities[2]. The purpose of this study is to identify possible biomarkers, associated pathways, and proteins by identifying differentially expressed genes in GC using microarray analysis.[3]
  • Methods: For the gene expression analysis, GSE54129 microarray dataset was analyzed by GEO2R online software. GEPIA2 [4] and ENCORI [5] online databases were used to validate the differential expression analysis. Also, the survival and co-expression analyses were performed by GEPIA2 and ENCORI. STRING [6] online software was performed to demonstrate the protein-protein interaction analysis. Pathway enrichment and gene ontology (GO) analysis was performed by enrichr [7]. Finding the possible dangerous single nucleotide polymorphisms (SNPs) in the 3’UTR region of selected genes was performed by miRNASNP [8]. Analysis of the potential deleterious SNPs in the coding sequence (CDS) of selected genes was performed by SIFT database [9].
  • Results: Based on microarray data analysis, INHBA has a significant up-regulation in the gastric cancer samples, compared to control (logFC: 4.6813, adj. P. Val < 0.0001). GEPIA2 and ENCORI expression analysis validates the expression analysis results. Based on survival analysis, the high expression of INHBA has a significant positive correlation with the low survival rate of GC patients (HR: 0.029, logrank p: 0.028). Based on enrichr, INHBA regulates the activin signaling pathway. SNP analysis revealed that rs1479520687 (G/A) inhibiting the interaction of hsa-miR-3928-5p with INHBA mRNA (ΔG binding: -11.78 kCal/mol). Protein-protein interaction analysis revealed that INHBA has significant protein interaction with ACVR2A, SMAD3, ACVRL1, and FST proteins.
  • Conclusion: Our findings revealed the overexpression of INHBA in GC; furthermore, this gene participates in some crucial cancer-related patways. Besides, this study suggests that it would probably play prognosis role in this cancer. Additional studies are required to validate our outcomes and enhance our insight about the function of INHBA in GC.
  • Keywords: bioinformatics, biomarker, systems biology, RNA interaction