TP73-AS1 rs3737589 Polymorphism is Associated With the Clinical Stage of Colorectal Cancer

OBJECTIVE: TP73-AS1 can promote the occurrence and development of a variety of tumors, including colorectal cancer (CRC). The current study aimed to investigate the association between a potentially functional genetic polymorphism (rs3737589 T > C) on the TP73-AS1 gene and the susceptibility and clinical stage of CRC in a Chinese Han population. METHODS: The polymorphic genotyping was performed by the SNaPshot method. The real-time quantitative PCR method and the luciferase assay were used separately to explore genotype-tissue expression and the function of the genetic polymorphism. RESULTS: A total of 576 CRC patients and 896 healthy controls were included in the current study. The rs3737589 polymorphism was not associated with CRC susceptibility but was associated with the CRC stage (CC vs. TT: OR = 0.25, 95% CI = 0.12 – 0.54, P=0.0003; C vs. T: OR = 0.69, 95% CI = 0.53–0.89, P=0.006; and CC vs. (TC + TT): OR = 0.26, 95% CI = 0.12–0.56, P=0.0004). CRC patients carrying the rs3737589 CC genotype or C allele were less likely to have stage III/IV tumors than those carrying the rs3737589 TT genotype or T allele. The expression of TP73-AS1 was lower in CRC tissues with the rs3737589 CC genotype compared to those with the TT genotype. Bioinformatics analysis and the luciferase assay revealed that the C allele could promote the binding of miR-3166 and miR-4771 to TP73-AS1. CONCLUSION: The TP73-AS1 gene rs3737589 polymorphism affecting miRNAs binding is associated with the CRC stage and may serve as a biomarker for predicting CRC progression.