Bioinformatics analysis of regulatory elements of the CD151 gene and insilico docking of CD151 with diallyl sulfide

Abstract

CD151 is a key player of cancer cell growth and metastasis and is highly deregulated in various cancers. Adenylate/uridylate-rich elements (AREs) and single nucleotide polymorphism (SNP) are the most common regulators in 3′Untranslatory regions (3′-UTRs) and determine the stability of mRNAs. RNAi-based screening has demonstrated that miRNAs are involved in ARE and SNP-mediated control of gene expression. Further, the combination of miRNAs and transcription factors (TFs) influence the expression of target genes. To identify miRNA candidates, TFs, ARE and SNPs of CD151 and to predict CD151 based anti-cancer agents for breast cancer. miRDB was used to identify CD151-associated miRNA candidates, AREsite was used to identify ARE in CD151 mRNA and SNPinfo Web Server was used to detect functional SNPs in CD151. The transcription factors (TFs) that regulate CD151 expression were predicted by TF2DNA database. Connectivity map (CMap) analysis was performed to screen potential anticancer agents against breast cancer. LibDoc was used to predict the interaction of diallyl sulfide with a large extracellular loop (LEL) of CD151. The results of the computational analysis showed that hsa-miR-3663-3p and hsa-miR-4763-3p are potential matured miRNAs of CD151. SNPs, rs1130716 and rs35042031 are found in the binding sites of hsa-miR-3663-3p and hsa-miR-4763-3p, respectively. CD151 has one AU-rich element, which could be involved in hsa-miR-3663-3p binding at 3′-UTR. Additionally, hsa-miR-3663-3p is found to interact with a transcription factor, ZNF519. CMap analysis identified diallyl sulfide as putative therapeutic agent for breast cancer. Further, diallyl sulfide is found to interact with LEL of CD151 and exhibited druglikeness property as per Lipinski rule of five. These findings will be useful for understanding the role of CD151 in breast cancer and to develop targeted therapeutics.