MAGI2-AS3 rs7783388 polymorphism contributes to colorectal cancer risk through altering the binding affinity of the transcription factor GR to the MAGI2-AS3 promoter.

Abstract

BackgroundIt has been indicated that the single nuclear polymorphisms (SNPs) in the long noncoding RNA (lncRNA) have association with colorectal cancer (CRC) susceptibility.MethodsWe enrolled 1078 cases with CRC and 1175 age‐ and gender‐matched cancer‐free controls to explore whether the polymorphisms in MAGI2‐AS3 have associations with CRC risk. qRT‐PCR, expression quantitative trait loci (eQTL) analyses, dual‐luciferase reporter assay, chromatin immunoprecipitation (ChIP), flow cytometry, and transwell assays were performed to explore the specific mechanisms in which MAGI2‐AS3 rs7783388 variation influenced the tumorigenesis of CRC.ResultsSubjects carrying rs7783388 GG genotype presented a higher risk of CRC compared with the AG/AA genotypes. Mechanistically, we found that the functional genetic variant of rs7783388 A > G decreased binding affinity of transcription factor glucocorticoid receptor (GR) to the MAGI2‐AS3 promoter, resulting in decreased transcriptional activity that subsequently downregulated MAGI2‐AS3 expression. Furthermore, functional experiments elucidated that MAGI2‐AS3 overexpression suppressed CRC cell proliferation, migration, and invasion capacities, arrested cell cycle at G0/G1 phase, and promoted cell apoptosis.ConclusionTaken together, our study demonstrated that the potential function of MAGI2‐AS3 as a tumor suppressor for CRC, and the MAGI2‐AS3 rs7783388 polymorphism is associated with the increased susceptibility to CRC by altering the binding ability of GR to the MAGI2‐AS3 promoter.