Potentially functional genetic variants in interferon regulatory factor family genes are associated with colorectal cancer survival.
Mol Carcinog
; 2024 May 30.
Article
en En
| MEDLINE
| ID: mdl-38812445
ABSTRACT
Interferon regulatory factor (IRF) family genes play a critical role in colorectal cancer (CRC) development and impact patient survival. This study evaluated the influence of functional single nucleotide polymorphisms (SNPs) in IRF genes on CRC survival, including functional predictions and experimental validations. Multivariate Cox regression analysis identified three linked SNPs as significant survival predictors, with the rs141112353 T/T genotype in the 3'UTR region of IRF6 significantly associated with decreased survival (HR = 1.60, P = 6E-04). Expression quantitative trait loci (eQTL) analysis indicated that the rs141112353 TA > T alteration reduced IRF6 expression. Dual luciferase assays showed lower activity for the T allele in the presence of hsa-miR-548ap-3p. Data from The Cancer Genome Atlas (TCGA) and other databases confirmed lower IRF6 levels in CRC tissues, correlating with worse survival and inversely with M2 macrophage infiltration. In vitro, IRF6 overexpression inhibited CRC cell proliferation and M2 macrophage polarization by downregulating MIF expression. These findings suggest that the IRF6 rs141112353 TA > T variant significantly affects CRC survival, potentially by enhancing miR-548-ap-3p binding affinity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Mol Carcinog
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
China