Rs56288038 (C/G) in 3'UTR of IRF-1 Regulated by MiR-502-5p Promotes Gastric Cancer Development

Abstract

Background/Aims: Interferon regulatory factor 1 (IRF-1) has been shown to function as a transcriptional activator or repressor of a variety of target genes. However, its upstream, non-coding RNA-related regulatory capacity remains unknown. In this study, we focus on the miRNA-associated single nucleotide polymorphisms (SNPs) in the 3′untranslated region (UTR) of IRF-1 to further investigate the functional relationship and potential diagnostic value of the SNPs and miRNAs among Chinese gastric cancer (GC) patients. Methods: We performed a case-control study with 819 GC patients and 756 cancer-free controls. Genotyping by realtime PCR assay, cell transfection, and the dual luciferase reporter assay were used in our study, and the 5-year overall survival rate and relapse-free survival rate in different groups were investigated. Results: We found that patients suffering from Helicobacter pylori (Hp) infection were the susceptible population compared to controls. SNP rs56288038 (C/G) in IRF-1 3′UTR was involved in the occurrence of GC by acting as a tumor promoter factor. SNP rs56288038 (C/G) could be up-regulated by miR-502-5p, which caused a down-regulation of IRF-1 in cell lines and decreased apoptosis induced by IFN-γ. Carrying the G genotype was related to significantly low expression of IRF-1 and Hp infection, poor differentiation, big tumor size, invasion depth, as well as the high probability of metastasis, and moreover, the C/G SNP was associated with shorter survival of GC patients with five years of follow-up study. Conclusions: our findings have shown that the SNP rs56288038 (C/G) in IRF-1 3′UTR acted as a promotion factor in GC development through enhancing the regulatory role of miR-502-5p in IRF-1 expression.

Keywords

• IRF-1
• MiR-502-5p
• 3′UTR
• Metastasis and survival