lncRNA TINCR SNPs and Expression Levels Are Associated with Bladder Cancer Susceptibility

Genet Test Mol Biomarkers. 2021 Jan;25(1):31-41. doi: 10.1089/gtmb.2020.0178. Epub 2020 Dec 28.

Abstract

Objective: The long-chain noncoding RNA (lncRNA) TINCR has been associated with the development and progression of bladder cancer. In this study, we analyzed the correlation between lncRNA TINCR single-nucleotide polymorphisms (SNPs) and bladder cancer susceptibility risk. Methods: The genotypes of the lncRNA TINCR rs2288947 and rs8113645 loci in 125 surgically treated bladder cancer patients and 125 controls were analyzed by Sanger sequencing. A dual-luciferase reporter gene assay was used to detect the binding of the microRNAs miR-1247-3p and miR-30c-2-3p with the lncRNA TINCR. The receiver operating characteristic curve was used to analyze the value of expression levels of the lncRNA TINCR and the microRNAs miR-1247-3p and miR-30c-2-3p in the diagnosis of bladder cancer. Results: The bladder cancer susceptibility risk of the rs2288947 G allele carriers was 2.32 times higher compared with the A allele carriers (95% confidence interval [CI]: 1.58-3.42, p < 0.01); The bladder cancer susceptibility risk of the rs8113645 T allele carriers was 0.33 times compared with the C allele carriers (95% CI: 0.19-0.55, p < 0.01). lncRNA TINCR was more highly expressed in bladder cancer tissues than controls (p < 0.01). The lncRNA TINCR rs2288947 A>G variation was associated with increased expression of lncRNA TINCR in bladder cancer tissues, and the rs8113645 C > T was associated with decreased expression. The expression levels of the lncRNA TINCR in cancer and paracancerous tissues showed a significant negative correlation with that of miR-1247-3p and miR-30c-2-3p (r = -0.89, -0.78, -0.81, and -0.66, all p < 0.01). The dual-luciferase reporter gene assay results indicate that the lncRNA TINCR rs2288947 G allele is the target of miR-1247-3p, and the rs8113645 C allele is the target of miR-30c-2-3p. Conclusion: The lncRNA TINCR rs2288947 A>G is associated with increased bladder cancer risk and rs8113645 C > T is associated with decreased susceptibility. These two SNP loci are associated with lncRNA TINCR expression levels; however, further studies are needed for validation.

Keywords: bladder cancer; lncRNA TINCR; miR-1247-3p; miR-30c-2-3p; single-nucleotide polymorphism.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • RNA, Long Noncoding* / biosynthesis
  • RNA, Long Noncoding* / genetics
  • RNA, Neoplasm* / biosynthesis
  • RNA, Neoplasm* / genetics
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / metabolism

Substances

  • RNA, Long Noncoding
  • RNA, Neoplasm
  • TINCR lncRNA, human