Abstract
The role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) and its functional single nucleotide polymorphisms (SNPs) in papillary thyroid carcinoma (PTC) is still largely unclear. Therefore, we investigated the involvement of lncRNA HOTAIR and its three haplotype-tagging SNPs (htSNPs) in PTC. There was higher expression of HOTAIR in PTC tissues compared to normal tissues. A series of gain-loss assays demonstrated that HOTAIR acts as a PTC oncogene via promoting tumorigenic properties of PTC cells. Additionally, the functional HOTAIR rs920778 genetic variant was a PTC susceptibility SNP. Subjects with the HOTAIR rs920778 TT genotype had an odds ratio (OR) of 1.88, 1.25 and 1.61 (P = 6.0 × 10−6, P = 0.028 and P = 3.2 × 10−5) for developing PTC in Shandong, Jiangsu and Jilin case-control sets compared with subjects with the CC genotype. This statistically significant associations were only found between the rs920778 genetic polymorphism and PTC risk in females but not in males. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was confirmed both in vitro and in vivo. Our results demonstrate that functional SNPs influencing lncRNA regulation may explain a part of PTC genetic basis.
Highlights
Considering the important involvement of genetic polymorphisms in regulating expression of HOTAIR, we investigated the association between three HOTAIR haplotype-tagging SNPs (htSNP) and papillary thyroid carcinoma (PTC) susceptibility in a case-control design
We investigated the oncogene role of lncRNA HOTAIR in PTC and the association between HOTAIR htSNPs and PTC risk through a two stage case-control approach
We found that the functional HOTAIR rs920778 single nucleotide polymorphisms (SNP) was a PTC susceptibility polymorphism in Chinese
Summary
We examined its expression in tissue specimens of PTC and normal thyroid tissues and elucidated its oncogene nature in PTC cells. We reported the functional significance of the lncRNA HOTAIR single nucleotide polymorphisms (SNP) in esophageal squamous cell carcinoma (ESCC) and gastric cancer[12,13]. On the basis of our previous findings, we hypothesized that the functional genetic variants in the HOTAIR gene may affect HOTAIR expression and influence consequential risk of developing PTC. To test this hypothesis, we genotyped three HOTAIR haplotype-tagging SNPs (htSNP) in three large independent case-control sets to examine the association between HOTAIR genotypes and PTC risk. The regulatory functions of the PTC susceptibility SNP rs920778 on HOTAIR expression was investigated in PTC cell lines and in patient tissue specimens
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
