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

Author(s)

Carron, Juliana ^[1] ; Dalla Costa, Ana Paula ^[2] ; Rinck-Junior, Jose Augusto ^[2] ; Mariano, Fernanda Viviane ^[3] ; Carvalho, Benilton de Sa ^[4] ; Passos Lima, Carmen Silvia ^[2] ; Lourenco, Gustavo Jacob ^[1]

Affiliation

^[1] Univ Estadual Campinas, Sch Med Sci, Lab Canc Genet, Rua Vital Brasil, 50, BR-13083888 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Sch Med Sci, Dept Internal Med, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Sch Med Sci, Dept Pathol, Campinas, SP - Brazil

^[4] Univ Estadual Campinas, Inst Math Stat & Sci Comp, Dept Stat, Campinas, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 OCT 12 2020.
• Web of Science Citations: 0

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 < 0.001) and higher levels of miR-4421 (p = 0.02). The miR-4421 showed more efficient binding with 3'-UTR of the variant G allele when compared with wild-type allele A (p = 0.001). Our data suggest that ERP29 rs7114 SNV may alter the risk and prognosis of OPSCC due to variation in the ERp29 production possibly modulated by miR-4421. (AU)

• FAPESP's process: 12/17182-1 - Polymorphic genes expression analysis identified in patients with squamous cell carcinoma of base of tongue
• Grantee: Gustavo Jacob Lourenço
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/18039-6 - Functional analysis of polymorphic genes in oropharyngeal squamous cell carcinoma
• Grantee: Carmen Silvia Passos Lima
• Support Opportunities: Regular Research Grants