• Has-miR-213-3p/NEAT1 axis of a ceRNA network promotes the development of pancreatic cancer by regulating Pi3k-Akt signaling pathway and TGF-beta signaling pathway: an integrated bioinformatics and systems biology analysis
  • MohammadHossein Teymouri,1 Mohammad Rezaei,2 Mansoureh Azadeh,3,*
    1. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    2. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    3. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran


  • Introduction: More than 90% of pancreatic cancer cases are pancreatic ductal adenocarcinoma (PDAC) with a 5-year survival rate of approximately only 5%. In recent decades, miRNAs and lncRNAs have been studied and are considered as impactful biomarkers in cancer. Therefore, in this bioinformatic approach, the goal was to spot and determine a biological network of genes, miRNAs and lncRNAs which have a notable influence on progression of PDAC.
  • Methods: To begin with, GSE15471 has been chosen from NCBI Gene Expression Omnibus (GEO) and was analyzed with R Studio in order to find genes with significant increase in expression regulation. INHBA, THBS2, NTM and SULF1 were selected and by using miRWalk database, plenty miRNAs were found for each of these genes. Furthermore, by using Venny 2.1 a mutual miRNA between these 4 genes was identified which was hsa-miR-214-3p. in addition, with the purpose of finding lncRNAs related to this network, the miRNA was searched in LncBase 3.0 and DLGAP1-AS1 and NEAT1 were selected as suitable lncRNAs. Ultimately, the pathways that these genes were involved in were analyzed and studied to find their role in Cancer. At last, Cystoscope software 3.8.2 was used to show the interaction between the components of the ceRNA network.
  • Results: Based on the analysis that were carried out, the mentioned 4 genes were selected and by using Kegg database their pathways were examined individually. INHBA is involved in Cytokine-cytokine receptor interaction, TGF-beta signaling pathway and Signaling pathways regulating pluripotency of stem cells. One of the most crucial pathways in which THBS2 has a role is PI3K-Akt signaling pathway which is consequential in development of cancer. With the shared miRNA with INHBA and THBS2 and lncRNAs that have interactions with it, NTM and SULF1 have increased expression levels as well and could have a role in cancer progression.
  • Conclusion: Contemplating the above paragraphs, it is concluded that INHBA, THBS2, NTM and SULF1 with has-miR-214-3p and its CeRNAs (competing endogenous RNAs) DLGAP1-AS1 and NEAT1 act as a biological network with important role in cell energy and growth pathways. Thus, these findings could provide a promising therapy method for treatment of PDAC patients.
  • Keywords: ceRNA - Systems biology - Pancreatic ductal adenocarcinom - Bioinformatics