Mutations in microRNA Binding Sites of CEP Genes Involved in Cancer

Abstract

The CEP genes play a pivotal role in the replication of the cell. CEP family proteins form the major constituents of the centrosome and play a prominent role in centriole biogenesis and in cell replication. Alteration in CEP genes will result in disruption of cell cycle that may in turn cause cancer. In our study, we found that 16 of the CEP genes are a potential target to miRNA that binds to complementary sequences in 3'untranslated regions (UTR) of mRNA and stop them from translation. Single nucleotide polymorphisms (SNPs) occurring naturally in such miRNA binding site can alter the miRNA: mRNA interaction and can significantly alter gene expression. We developed a systematic computational pipeline that integrates data from well-established databases, followed stringent selection criteria and identified a panel of 44 high-confidence SNPs that may impair miRNA target sites in the 3'UTR of 16 genes. Further we performed expression analysis to shed light on the potential tissues that might be affected by mutation, enrichment analysis to find the metabolic functions of the gene, and network analysis to highlight the important interactions of CEP genes with other genes to provide insight that complex network will be disturbed upon mutation. In this study, we explored and prioritised the SNPs in CEP gene which could act as a potential target in centrosome-associated human disease. Our analysis would provide a thoughtful insight to wet lab researches to understand the expression pattern of CEP genes and binding phenomenon of mRNA and miRNA upon mutation, which is responsible for inhibition of translation process at genomic levels.

MicroRNA expression in cervical cancer: Novel diagnostic and prognostic biomarkers

“…8 Computer technology analysis objectively demonstrated the mutation of the miRNA binding site involved in cancer and the mechanism of gene regulation mediated by it. [9][10][11] In addition, miRNAs are aberrantly expressed in various types of malignancies and function either as oncogenes or tumor suppressors. 12 Therefore, exploring relevant miRNA mechanisms plays a significant role in the diagnosis, prognosis, and personalized targeted therapy of tumors.…”

Circulating Extracellular Vesicle MicroRNA as Diagnostic Biomarkers in Early Colorectal Cancer—A Review

“…One of the most extensively studied classes of EV cargo to date has been miRNA, which are single-stranded, non-coding RNA molecules of approximately 18-22 nucleotides [60]. miRNA have been implicated in a host of normal biochemical processes, including cell differentiation, proliferation, and apoptosis [60][61][62][63].…”

MicroRNA‐binding site polymorphisms and risk of colorectal cancer: A systematic review and meta‐analysis

“…miRNA‐binding sites are conserved through evolution and contain lesser polymorphisms . Polymorphisms in these sites can affect miRNA:mRNA interactions and target mRNA expression . In one study, the association between let‐7 miRNA‐binding site polymorphisms and CRC outcome has been described, based on one miRNA, one database (PubMed), and also CRC risk was not investigated .…”

“…23 Polymorphisms in these sites can affect miRNA:mRNA interactions and target mRNA expression. 24,25 In one study, the association between let-7 miRNA-binding site polymorphisms and CRC outcome has been described, based on one miRNA, one database (PubMed), and also CRC risk was not investigated. 26 miRNAs' target site polymorphisms may potentially play a role in the interaction between miRNAs and their target mRNA, which is dependent on the effect of polymorphism on miRNA:mRNA interactions.…”