The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population

Abstract

The HOX transcript antisense intergenic RNA (HOTAIR), a well-known long noncoding RNA, is involved in pathogenesis and progress of multiple tumors. Its ectopic expression and biological functions have been observed in gastric cancer. In this study, we conducted a two-stage case-control study to evaluate whether genetic variations of HOTAIR were associated with gastric cancer risk. We identified that a single nucleotide polymorphism (SNP) rs4759314 was significantly associated with the increased gastric cancer risk with an odds ratio (OR) of 1.39 [95% confidence interval (CI) = 1.13-1.71, P = 0.002] in the combined sets. Further functional experiments revealed the allele-specific effects on HOTAIR and HOXC11 expressions in gastric cancer tissues, of which HOTAIR and HOXC11 expressions of individuals carrying with AG genotype were much higher than those with AA genotype; similarly, the effects occurred in intronic promoter activities, of which the promoter activity of G allele was more pronounced than that of A allele. Interestingly, we identified a novel potential oncogene HOXC11 in gastric cancer pathogenesis with differential expression in gastric cancer tissues by association analysis with candidate gene strategy. These results suggest that SNP rs4759314 of HOTAIR acts as a potential biomarker for predicting gastric cancer, and the role of HOXC11 in gastric cancer etiology is warranted to further investigation.

Keywords: HOTAIR; gastric cancer; genetic variants; long noncoding RNA.

Figure 1. Subgroup analysis of demographic features for the association between SNP rs4759314 and gastric cancer risk in genetic dominant model

The red diamonds and blue horizontal lines correspond to the subgroup-specific OR and 95% CI; the orange diamonds represents the pooled OR with 95% CI.

Figure 2. The allele-specific effects of SNP rs4759314 on HOTAIR and HOXC11 expression in 63 gastric cancer tissues and allele-specific promoter activity

The allele-specific effects showed significantly on HOTAIR a. and HOXC11 b. The expression of HOTAIR and HOXC11 presented a slight correlation in gastric cancer tissues c. expression level, as well on the intronic promoter activity d.