• miR-520a-5p and lncRNA CRNDE regulates the expression level of ADAMTS5 as the novel up-reglated non-coding RNAs in the Degradation of the extracellular matrix signaling pathway: Integrated systems biology and experimental investigation on breast cacer patients
  • Mojdeh Mahmoudian,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: A new gene family of proteins known as a disintegrin and metalloproteinases (ADAMs) has similarities in sequence to the reprolysin family of snake venomases and shares the metalloproteinase domain with matrix metalloproteinases (MMPs). Based on their structural similarity, they are separated into two classes: membrane-anchored ADAM and ADAM with thrombospondin motifs (ADAMTS). The biological processes of membrane protein shedding, proteolysis, cell adhesion, cell fusion, and cell migration are all impacted by these molecules. In this study, we performed an integrated systems biology approach to find the related competitive endogenous RNA network, regulating ADAMTS5 in the breast cancer (BC) patients.
  • Methods: The RNA interaction analysis tools miRWalk, lncRRisearch, ENCORI, and lncBase3 as well as the protein interaction analysis tool STRING were used in this investigation. ENCORI and GEPIA2 carried out assessments of survival, expression, and correlation. Microarray analysis also carries out expression analysis. Enrichr online software was used to find the gene ontology (GO) and pathways related to selected genes
  • Results: Based on microarray analysis, GEPIA2, and ENCORI online databases, ADAMTS5 has a significant low-expression in the BC samples (logFC: -3.791881, adj. P. Val < 0.0001). hsa-miR-520a-5p has a significant interaction with the ADAMTS5 in the 5UTR region of mRNA (score: 1). miR-520a-5p has a significant up-regulation in the BC patients (Fold Change: 2.16, FDR: 0.05). lncRNA interaction analysis revealed that lncRNA CRNDE has a significant interaction with ADAMTS5. CRNDE has a significant up-regulation in the BC patients (FC: 1.30, FDR: 0.0001). Based on pathway enrichment analysis, ADAMTS5 regulates the Degradation of the extracellular matrix signaling pathway. Mentioned gene regulates negative regulation of metabolic process in endoplasmic reticulum lumen.
  • Conclusion: miR-520a-5p might modulate the Degradation of the extracellular matrix signaling pathway in the BC patients by regulation of the expression level of ADAMTS5. lncRNA CRNDE also regulates the expression of ADAMTS5 as a significantly up-regulated lncRNA. Mentioned RNA could be considered as the novel biomarkers in the BC diagnosis.
  • Keywords: Bioinfomatics, Systems Biology, RNA interaction, Breast Cancer, Gene Expression Profiling