Functional polymorphisms in LncRNA HOTAIR contribute to susceptibility of pancreatic cancer

BackgroundPancreatic cancer (PC) remains one of the most aggressive cancers worldwide. However, genetic factors underlying PC susceptibility remain largely unclear. Long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) acts as an oncogene and its genetic variation has been linked to many cancers. However, the associations between genetic variants in HOTAIR gene and PC risk has not yet been reported.MethodsA two-stage, case-control study was conducted to investigate the associations between HOTAIR SNPs and the PC risk. Dual luciferase reporter assay and real-time -PCR (RT-PCR) was conducted to evaluate the potential regulatory function of HOTAIR rs4759314 and rs200349340.ResultsWe found the minor alleles of rs4759314 (OR=1.76; 95 CI 1.37-2.25; P=0.001) and rs200349340 (OR=1.32; 95 CI 1.12-1.56; P=0.001) were significantly associated with PC susceptibility. In functional experiments, we found subjects carrying the minor alleles of rs4759314 and rs200349340 had significantly higher HOTAIR RNA levels (meanSD) than those carrying the major alleles in PC tissues. For rs4759314, cells transfected with rs4759314 -G allele construct showed higher relative luciferase activity; while for rs200349340, cells transfected with rs200349340 -G allele construct showed more sensitive change of the relative luciferase activity.Conclusion Our studies revealed that functional SNP rs4759314 and rs200349340 of HOTAIR had strong associations with PC susceptibility. These findings elucidate that functional genetic variants influencing lncRNA expression may explain a portion of PC genetic basis.