A functional Cis-eQTL locus in lncRNA ZNRD1-AS1 contributes to the susceptibility of endometrial cancer.

OBJECTIVE

Endometrial cancer (EC) remains one of the most common gynecologic malignancies worldwide. However, the exact etiology is still unknown. Human Zinc ribbon domain containing 1 (ZNRD1) was involved in carcinogenesis and progression of multiple cancers, including EC. ZNRD1-AS1, a long noncoding RNA (lncRNA) located in the upstream of ZNRD1, has been reported as an essential component in carcinogenesis. However, the underlying relations of ZNRD1-AS1 with development of EC remain obscure. This study aims to evaluate the potential role of ZNRD1-AS1 and Cis-eQTL loci of ZNRD1 in the occurrence of EC.

PATIENTS AND METHODS

We first evaluated the expression of ZNRD1-AS1 and ZNRD1 among EC tissues and corresponding normal tissues using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, to reveal the underlying mechanisms, we investigated the associations between Cis-eQTL loci of ZNRD1 in ZNRD1-AS1 and the susceptibility of EC. Further, in vitro experiments were conducted to evaluate the regulation role of rs9261204 on the expression of ZNRD1gene.

RESULTS

Higher expression of ZNRD1-AS1 and lower expression of ZNRD1 were detected in the EC tissues, compared to the normal tissues. Minor allele of rs9261204 was significantly associated with increased risk of EC (OR: 1.31; 95% CI: 1.08-1.6; p=0.007) [corrected]. Furthermore, in vitro experiments confirmed that Ishikawa cells with rs9261204 G allele had lower mRNA level of ZNRD1, compared to the A allele.

CONCLUSIONS

Our findings first showed the contribution of LncRNA ZNRD1-AS1 and Cis-eQTL loci of ZNRD1 to the development of EC. Further studies incorporating larger populations and functional assays are warranted.