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Role of a genetic variation in the microRNA-4421 binding site of ERP29 regarding risk of oropharynx cancer and prognosis.

ABSTRACT: We conducted a two-stage association study on patients with oropharynx (OP) squamous cell carcinoma (SCC) and healthy controls to identify single nucleotide variants (SNVs) located at the microRNA (miR)-binding sites of carcinogenesis genes associated with risk and prognosis of the disease. In stage 1, 49 patients and 49 controls were analyzed using Genome-Wide Human SNV Arrays to identify variants in the 3'-untranslated region (3'-UTR) of carcinogenesis-related genes, and one SNV was selected for data validation in stage 2 by TaqMan assays in 250 OPSCC patients and 250 controls. The ERP29 c.*293A?>?G (rs7114) SNV located at miR-4421 binding site was selected for data validation among 46 SNVs. The ERp29 and miR-4421 levels were evaluated by quantitative-PCR and Western blotting. Interaction between miR-4421 with 3'-UTR of ERP29 was evaluated by luciferase reporter assay. Event-free survival (EFS) was calculated by Kaplan-Meier and Cox methods. ERP29 GG variant genotype was more common in OPSCC patients than in controls (6.4% vs 3.6%, p?=?0.02; odds ratio: 5.67; 95% confidence interval (CI) 1.27-25.26). Shorter EFS were seen in the base of tongue (BT) SCC patients with GG genotype (0.0% vs 36.2%, p?=?0.01; hazard ratio: 2.31; 95% CI: 1.03-5.15). Individuals with ERP29 AG or GG genotypes featured lower levels of ERP29 mRNA (p?=?0.005), ERp29 protein (p?

SUBMITTER: Carron J

PROVIDER: S-EPMC7550560 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Role of a genetic variation in the microRNA-4421 binding site of ERP29 regarding risk of oropharynx cancer and prognosis.

Carron Juliana J Costa Ana Paula Dalla APD Rinck-Junior José Augusto JA Mariano Fernanda Viviane FV de Sá Carvalho Benilton B Lima Carmen Silvia Passos CSP Lourenço Gustavo Jacob GJ

Scientific reports 20201012 1

We conducted a two-stage association study on patients with oropharynx (OP) squamous cell carcinoma (SCC) and healthy controls to identify single nucleotide variants (SNVs) located at the microRNA (miR)-binding sites of carcinogenesis genes associated with risk and prognosis of the disease. In stage 1, 49 patients and 49 controls were analyzed using Genome-Wide Human SNV Arrays to identify variants in the 3'-untranslated region (3'-UTR) of carcinogenesis-related genes, and one SNV was selected f ...[more]

PMID: 33046743

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Project description:Micro-RNA (miRNA or miR) regulates at least 60% of the genes in the human genome through their target sites at mRNA 3'-untranslated regions (UTR), and defects in miRNA expression regulation and target sites are frequently observed in cancers. We report here a systematic analysis of the distribution of miRNA target sites. Using the evolutionarily conserved miRNA binding sites in the TargetScan database (release 7.1), we constructed a miRNA co-regulation network by connecting genes sharing common miRNA target sites. The network possesses characteristics of the ubiquitous small-world network. Non-hub genes in the network-those sharing miRNA target sites with small numbers of genes-tend to form small cliques with their neighboring genes, while hub genes exhibit high levels of promiscuousness in their neighboring genes. Additionally, miRNA target site distribution is extremely uneven. Among the miRNAs, the distribution concentrates on a small number of miRNAs, in that their target sites occur in an extraordinarily large number of genes, that is, they have large numbers of target genes. The distribution across the genes follows a similar pattern; the mRNAs of a small proportion of the genes contain extraordinarily large numbers of miRNA binding sites. Quantitatively, the patterns fit into the P(K) ? K-? relationship (P(K): the number of miRNAs with K target genes or genes with K miRNA sites; ?: a positive constant), the mathematical description of connection distribution among the nodes and a defining characteristic of the so-called scale-free networks-a subset of small-world networks. Notably, well-known tumor-suppressive miRNAs (Let-7, miR-15/16, 26, 29, 31, 34, 145, 200, 203-205, 223, and 375) collectively have more than expected target genes, and well-known cancer genes contain more than expected miRNA binding sites. In summary, miRNA target site distribution exhibits characteristics of the small-world network. The potential to use this pattern to better understand miRNA function and their oncological roles is discussed.

Dataset Information

Role of a genetic variation in the microRNA-4421 binding site of ERP29 regarding risk of oropharynx cancer and prognosis.

Publications

Role of a genetic variation in the microRNA-4421 binding site of ERP29 regarding risk of oropharynx cancer and prognosis.

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