Polymorphism of TUSC7 associated with gastric cancer susceptibility and binding with miR-133a-3p: a population-based case-control study

Int J Clin Oncol. 2021 Apr 22. doi: 10.1007/s10147-021-01924-w. Online ahead of print.


BACKGROUND: Previous studies have demonstrated that gene polymorphism is associated with cancer susceptibility. Most of these genes are involved in neoplastic processes. Previous studies demonstrated that tumor-suppressor candidate 7 (TUSC7) was a tumor-suppressor gene in various tumors. This study aims to explore the association between lncRNA TUSC7 polymorphism and gastric cancer susceptibility and the potential function.

METHODS: The tagging SNPs of TUSC7 were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a Chinese Han population-based case-control study. The relative expression level of TUSC7 in plasma was conducted by quantitative real-time PCR (qRT-PCR). The gene-environment interaction was analyzed by multifactor dimensionality reduction (MDR). The dual luciferase reporter assay was used to examine whether SNP rs12494960 of TUSC7 allele variation affected the binding of lncRNA-TUSC7 and miRNAs miR-133a-3p.

RESULTS: Three tagging SNPs (rs12494960, rs1518338, rs2867837) of TUSC7 were selected to validate in population. The unconditional multiple logistic regression showed that individuals with genotype AA (OR: 1.79, 95% CI: 1.16, 2.70) of rs12494960 and GG (OR: 2.24, 95% CI: 1.12, 4.46) of rs2867837 in TUSC7 had increased risk of GC susceptibility. The qRT-PCR showed that CA and AA genotype of rs12494960 in TUSC7 had significantly lower relative expression level in plasma, compared with CC genotype. The dual luciferase reporter assay showed that TUSC7 and miR-133a-3p had interaction.

CONCLUSION: The mutant genotype of rs12494960 could increase the susceptibility of gastric cancer and might affect the corresponding mRNA expression of lncRNA TUSC7 in plasma.

PMID:33886026 | DOI:10.1007/s10147-021-01924-w