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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: BACKGROUND:It has been indicated that the single nuclear polymorphisms (SNPs) in the long noncoding RNA (lncRNA) have association with colorectal cancer (CRC) susceptibility. METHODS:We 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. RESULTS:Subjects 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. CONCLUSION:Taken 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.

SUBMITTER: Yang X

PROVIDER: S-EPMC7595890 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Yang Xi X Wu Shenshen S Li Xiaobo X Yin Ying Y Chen Rui R

Journal of clinical laboratory analysis 20200612 10

<h4>Background</h4>It has been indicated that the single nuclear polymorphisms (SNPs) in the long noncoding RNA (lncRNA) have association with colorectal cancer (CRC) susceptibility.<h4>Methods</h4>We 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), fl ...[more]

PMID: 32533587

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Project description:BackgroundProstate cancer (PCa) is the second most common cause of cancer-related deaths in American men. Even though increasing evidence has disclosed the competitive endogenous RNA (ceRNA) regulatory networks among cancers, the complexity and behavior characteristics of the ceRNA network in PCa remain unclear. Our study aimed to investigate the forkhead box A1 (FOXA1)-related ceRNA regulatory network and ascertain potential prognostic markers associated with PCa.MethodsRNA sequence profiles downloaded from The Cancer Genome Atlas (TCGA) were analyzed to recognize differentially expressed genes (DEGs) derived from tumor and non-tumor adjacent samples as well as FOXA1low and FOXA1high tumor samples. The enrichment analysis was conducted for the dysregulated mRNAs. The network for the differentially expressed long non-coding RNA (lncRNA)-associated ceRNAs was then established. Survival analysis and univariate Cox regression analysis were executed to determine independent prognostic RNAs associated with PCa. The correlation between DUSP2 and immune cell infiltration level was analyzed. Tissue and blood samples were collected to verify our network. Molecular experiments were performed to explore whether DUSP2 is involved in the development of PCa.ResultsA ceRNA network related to FOXA1 was constructed and comprised 18 lncRNAs, 5 miRNAs, and 44 mRNAs. The MAGI2-AS3~has-mir-106a/has-mir-204~DUSP2 ceRNA regulatory network relevant to the prognosis of PCa was obtained by analysis. We markedly distinguished the MAGI2-AS3/DUSP2 axis in the ceRNA. It will most likely become a clinical prognostic model and impact the changes in the tumor immune microenvironment of PCa. The abnormal MAGI2-AS3 expression level from the patients' blood manifested that it would be a novel potential diagnostic biomarker for PCa. Moreover, down-expressed DUSP2 suppressed the proliferation and migration of PCa cells.ConclusionsOur findings provide pivotal clues to understanding the role of the FOXA1-concerned ceRNA network in PCa. Simultaneously, this MAGI2-AS3/DUSP2 axis might be a new significant prognostic factor associated with the diagnosis and prognosis of PCa.

Dataset Information

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

Publications

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

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