Single nucleotide polymorphisms in microRNA binding sites on the HOX genes regulate carcinogenesis: An in-silico approach

Homeobox proteins, encoded by HOX genes, are transcriptional factors playing a crucial role in the master regulatory pathway in the cells. Any mutations in HOX genes will affect the expression of its allied proteins. Such mutations were correlated to the development of different cancer types. In this study, we found 15 HOX genes with a potential target to miRNA, which regulates the translation of the protein by binding to its mRNA through the 3′UTR region. Single nucleotide polymorphisms (SNPs) in this binding region could drastically affect the protein expression by affecting the number and the stability of miRNA-mRNA complexes. We found 77 miRNAs in 15 genes which were found to have altered binding efficiency because of 26 SNPs. After which, we tried to evaluate the impact of each of these SNPs on related HOX genes. Some SNPs such as SNP 15689 on the HOXB7 gene will decrease gene expression by creating or enhancing new binding sites for miRNA to mRNA, while other SNPs such as SNP 872760 on the HOXB5 gene will overexpress the gene by breaking or decreasing existing binding sites from miRNA to mRNA. Then we conducted an expression analysis to compare the mRNA expression profiles in normal and cancer tissue. Subsequently, we did an enrichment analysis followed by a network analysis to shed light on the metabolic function of the gene that could be affected by mutation and whether these mutations may affect other genes. For the first time, this study delivers information on the possible epigenetic regulation of HOX genes via the 77 miRNAs that have predicted target binding sites on HOX mRNAs, and SNPs may regulate those. Furthermore, we show that the HOX gene misregulation may influence other HOX and non-HOX genes, based on network analysis.