• SMAD5/hsa-miR-28-5p/ FTX CeRNA axis affects colorectal cancer development by regulating " TGF-beta signaling pathway": bioinformatics gene expression profiling and RNA interaction analysis
  • MahsaSadeghi,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: Colorectal cancer (CRC) is one of the most common malignant diseases in the world, and its incidences increased with age. Colorectal cancer develops slowly but can spread to surrounding and distant tissues of the body. Approximately 95 percent of colorectal cancers involve the glandular cells in the wall of the colon and are called adenocarcinomas. Other colorectal cancers may begin among hormone-producing cells, immune cells, or underlying connective tissue. Competitive endogenous RNAs (ceRNAs) theory have revealed a new mechanism of interaction between RNAs (mRNAs, miRNAs and lncRNAs) that is used to find the involved genes. In this study we used microarrays to detail the global programe of gene expression underlying different lines and stages of patient-derived colorectal cancer organoids to target novel biomarkers for diagnosis and curing CRC.
  • Methods: First, GSE117548 were downloaded from NCBI Gene Expression Omnibus (GEO) and analyzed using limma package to identify differentially expressed genes (DEGs) in different stages which are screened by RStudio software. SMAD5, DUSP4, PHLDA1 and IGF2 with these conditions (|logFC| > 2 and adjusted p-value< 0.05) were taken to the miRWalk 2.0 database to select the miRNAs related to the gene, next in LncBase v.3 miRNAs were searched and several lncRNAs were found which is called FTX, APTR,DLEU1 and H19. The binding and paring scores of these microRNAs have been studied which the interaction of them have been showed as a Cystoscope software.
  • Results: In the end, after analysis of total RNA from 16 human patient-derived colorectal cancer organoids. we obtained 264 DEGs composed of 78 upregulated and 186 downregulated genes. This analysis outcomes assigned that the GSE117548 were surprisingly enriched in several biological mechanisms. The candidate hub genes were searched in Kyoto Encyclopedia of Genes and Genomes (KEGG) database to find the pathways which they are participated in separately. Upregulated gene pointed CRC-related pathways named, TGF-beta signaling pathway which is named SMAD5 that illustrates as a vital gene of these pathways.
  • Conclusion: we measured differential expression genes in stage 3 to stage 4 of this cancer to find the invasion of cells and prevent metastasis. Several lines of evidence suggest that SMAD5 and PHLDA1 have an important role in cancer. SMAD5 is a Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase and also involved in Signaling pathways regulating pluripotency of stem cells. PHLDA1 is a potential transcriptional activator that acts as a modulator of apoptosis and cell proliferation so The results of this study indicate that there might be a CeRNA network between SMAD5, DUSP4, PHLDA1 and hsa-miR-28-5p.moreover, the presence of SMAD5 and PHLDA1 in this network , reinforces the possibility of PHLDA1 being a reliable biomarker for detect the metastasis of cancerous cells.
  • Keywords: Microarray, Colorectal cancer, PHLDA1, SMAD5, Bioinformatics, CeRNA, Systems biology,FTX