title: Association of Long Non-Coding RNA HOTAIR Polymorphisms with Cervical Cancer Risk in a Chinese Population.
abstract: Long non-coding RNAs (lncRNAs), HOTAIR has been reported to be upregulated in cervical cancer development and progression. However, SNPs (single nucleotide polymorphisms) in the lncRNAs and their associations with cervical cancer susceptibility have not been reported. In the current study, we hypothesized that SNPs within the lncRNA HOTAIR may influence the risk of cervical cancer. We performed a case-control study including 510 cervical cancer patients (cases) and 713 cancer-free individuals (controls) to investigate the association between three haplotype-tagging SNPs (rs920778, rs1899663 and rs4759314) in the lncRNA HOTAIR and the risk of cervical cancer. We found a strong association between the SNP rs920778 in the intronic enhancer of the HOTAIR and cervical cancer (P<10-4). Moreover, the cervical cancer patients with homozygous TT genotype were significantly associated with tumor-node-metastasis (TNM) stage. In vitro assays with allele-specific reporter constructs indicated that the reporter constructs bearing rs920778T allele conferred elevated reporter gene transcriptional activity when compared to the reporter constructs containing rs920778C allele. Furthermore, HOTAIR expression was higher in cervical cancer tissues than that in corresponding normal tissues, and the high expression was associated with the risk-associated allele T. In summary, our studies provide strong functional evidence that functional SNP rs920778 regulates HOTAIR expression, and may ultimately influence the predisposition for cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Liangsheng
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xueguan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Clincal Skills Training Center, The Second Hospital of Jilin University, Changchun, China.
authors.forename: Xianying
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002681:China; D004742:Enhancer Elements, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger