SNPs in 3′UTR miRNA Target Sequences Associated with Individual Drug Susceptibility

Abstract

The complementary interaction of microRNAs (miRNAs) with their binding sites in the 3′untranslated regions (3′UTRs) of target gene mRNAs represses translation, playing a leading role in gene expression control. MiRNA recognition elements (MREs) in the 3′UTRs of genes often contain single nucleotide polymorphisms (SNPs), which can change the binding affinity for target miRNAs leading to dysregulated gene expression. Accumulated data suggest that these SNPs can be associated with various human pathologies (cancer, diabetes, neuropsychiatric disorders, and cardiovascular diseases) by disturbing the interaction of miRNAs with their MREs located in mRNA 3′UTRs. Numerous data show the role of SNPs in 3′UTR MREs in individual drug susceptibility and drug resistance mechanisms. In this review, we brief the data on such SNPs focusing on the most rigorously proven cases. Some SNPs belong to conventional genes from the drug-metabolizing system (in particular, the genes coding for cytochromes P450 (CYP 450), phase II enzymes (SULT1A1 and UGT1A), and ABCB3 transporter and their expression regulators (PXR and GATA4)). Other examples of SNPs are related to the genes involved in DNA repair, RNA editing, and specific drug metabolisms. We discuss the gene-by-gene studies and genome-wide approaches utilized or potentially utilizable to detect the MRE SNPs associated with individual response to drugs.

miR-128-3p Regulates Follicular Granulosa Cell Proliferation and Apoptosis by Targeting the Growth Hormone Secretagogue Receptor

“…miRNAs can regulate the expression of target genes by influencing the stability of target gene mRNAs or blocking the translation process to exert their functions [ 48 , 49 , 50 ]. This study demonstrated that miR-128-3p in KGN cells can target GHSR to inhibit the expression of GHSR proteins.…”

Finding the Common Single-Nucleotide Polymorphisms in Three Autoimmune Diseases and Exploring Their Bio-Function by Using a Reporter Assay

“…Thus, based on ethnic differences, the findings may only apply to the Taiwanese population. Additionally, because the materials of the reporter assay used in the promoter–reporter cannot be shared with the 3’UTR-reporter, and the 3’UTR-reporter assay needs to consider the influence of microRNA [ 46 ], only the promoter region was discussed in this study.…”

miR-4716–3p and the target AKT2 Gene/rs2304186 SNP are associated with blood cancer pathogenesis in Pakistani population

“…miR-218 epigenetic silencing influenced by Rictor upregulation initiates the mTOR-Akt signaling cascade, thereby contributing to oral carcinogenesis [ 16 ]. The 3′UTRs miRNA recognition elements (MREs) of genes often have single nucleotide polymorphisms (SNPs) that modify the target microRNA binding affinity resulting in gene expression dysregulation [ 17 ]. Ovarian cancer patients with the 3′ UTR rs4245739 SNP have a reduced chance of survival because it creates an unsuitable target site for miR-191.…”