Association of Functional Genetic Variants of HOTAIR with Hepatocellular Carcinoma (HCC) Susceptibility in a Chinese Population

Abstract

Background/Aims: The HOX transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), plays an important role in the pathogenesis and progression of multiple tumors. The aim of the present study was to evaluate whether common single nucleotide polymorphisms (SNPs) in HOTAIR are related to hepatocellular carcinoma (HCC) susceptibility in a Chinese population. Methods: We genotyped three SNPs of HOTAIR in a hepatocellular carcinoma (HCC) case-control study, including 482 cases and 520 control subjects. SNPs were genotyped using real-time polymerase chain reaction (RT-PCR). Associations between gene polymorphisms and HCC were evaluated using multiple logistic regression analysis. The allele-specific effects on HOTAIR expression in HCC were confirmed by real time quantitative PCR and luciferase activity assays. The influence of HOTAIR SNPs on the proliferation of HCC cells was evaluated using a CCK-8 assay. Results: Significant associations were observed between the HOTAIR rs920778 C>T polymorphism and HCC risk (TT versus CC: OR = 1.634, 95% CI =1.028-2.598, P = 0.046) and the allelic model (allele T versus allele C: OR =1.293, 95% CI = 1.060-1.577, P = 0.011). However, no statistically significant differences of rs4759314 and rs1899663 genotypes were observed between patients and controls (both P > 0.05). The increased risk for rs920778 TT genotype carriers was more evident in a sub-group of drinkers (OR = 3.103, 95% CI = 1.151-8.368, p=0.025) and in people positive for HBV infection (OR = 2.885, 95% CI = 1.086-7.663, p=0.034). RT-PCR and luciferase activity assay confirmed that the rs920778 TT genotype induced significantly higher HOTAIR levels than did the CC genotype (P < 0.05). CCK-8 assays and colony formation assays demonstrated that the rs920778 TT genotype had a higher proliferation rate of HCC cells than did the CC genotype (P < 0.05). Conclusion: These results suggest that SNP rs920778 of HOTAIR acts as a potential biomarker for predicting hepatocellular carcinoma, and further studies are warranted to confirm these findings.