Strong evidence for LncRNA ZNRD1-AS1, and its functional Cis- eQTL locus contributing more to the susceptibility of lung cancer

Abstract

Long noncoding RNAs (IncRNAs), involved in cancer biology, contributing to essential cancer cell functions such as proliferation, invasion, and metastasis, have received increasing attention recently. Human Zinc ribbon domain containing 1 (ZNRD1) has been confirmed to be involved in carcinogenesis and development of multiple cancers. ZNRD1-AS1, a lncRNA in the upstream region of ZNRD1 which could down-regulate the expression of ZNRD1, has been identified as a possible component in carcinogenesis. The underlying relations of ZNRD1-AS1 with lung cancer development and metastasis remain obscure. In current study, we first evaluated the expression ZNRD1-AS1 and ZNRD1 among lung cancer tissues and corresponding normal tissues, which showed higher expression of ZNRD1-AS1 and lower expression of ZNRD1. To reveal the underlying mechanisms, we then investigated the associations between ZNRD1 eQTLs SNPs in ZNRD1-AS1 and risk of lung cancer in Han Chinese populations. G allele of SNP rs9261204 was significantly associated with an increased risk of lung cancer when compared with A allele (OR: 1.45; 95% CI: 1.19–1.75; P = 1.06 × 10^–4). A weaker, but similar effect was also observed in bladder cancer. SNP rs3757328 was also associated with increased risk of lung cancer (OR: 1.34; 95% CI: 1.07–1.67; P = 0.011). Our findings first confirmed the contribution of LncRNA ZNRD1-AS1 to the development of lung cancer in Asian population.