Long Noncoding RNA HULC Promoter Polymorphism rs1041279 Is Associated with an Increased Risk of Cervical Squamous Cell Carcinoma.

Abstract

Hepatocellular carcinoma upregulated long noncoding RNA (HULC), identified as an oncogene in cervical cancer, is involved in not only the clinical stage, lymph node metastasis, and depth of cervical invasion but also outcome. In this study, we aimed to investigate the association between 3 polymorphisms (i.e., rs1041279, rs3005167, and rs7770772) in the promoter of HULC and the risk of cervical squamous cell carcinoma (CSCC). The polymorphisms were genotyped using the multiplex ligase detection reaction assay. The promoter activity was measured using the dual-luciferase reporter assay kit. The rs1041279 GG genotype and G allele revealed a significantly higher risk of CSCC compared with the rs1041279 CC genotype and C allele (GG vs. CC, adjusted OR = 1.79, 95% CI, 1.17-2.73, P = 0.007; G vs. C, adjusted OR = 1.36, 95% CI, 1.09-1.69, P = 0.006). Haplotype analysis revealed that the rs3005167C-rs7770772G-rs1041279C or rs3005167C-rs7770772G-rs1041279G haplotype had a significantly higher risk of CSCC compared to the rs3005167G-rs7770772G-rs1041279C haplotype (CGC vs. GGC, OR = 2.38, 95% CI, 1.53-3.75, P < 0.001; CGG vs. GGC, OR = 3.76, 95% CI, 2.12-6.68, P < 0.001). Dual-luciferase reporter assay showed that the rs1041279 G promoter resulted in higher transcriptional activity compared with the rs1041279 C (P < 0.01). Additionally, the rs1041279 GG genotype carriers had an increased level of HULC expression (P = 0.03). These findings suggest that the HULC rs1041279 may be a useful marker for the etiology of CSCC.