机构:[1]Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China,[2]Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China,[3]Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China,[4]Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China,[5]Clincal Skills Training Center, The Second Hospital of Jilin University, Changchun, China
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.
基金:
Suzhou Science and Technology Agency grant (SYS201553, Dr. Min Hu)
第一作者机构:[1]Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China,
通讯作者:
通讯机构:[1]Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China,[2]Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China,[3]Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China,
推荐引用方式(GB/T 7714):
Liangsheng Guo,Xueguan Lu,Lijun Zheng,et al.Association of Long Non-Coding RNA HOTAIR Polymorphisms with Cervical Cancer Risk in a Chinese Population[J].PLOS ONE.2016,11(7):e0160039.doi:10.1371/journal.pone.0160039.
APA:
Liangsheng Guo,Xueguan Lu,Lijun Zheng,Xianying Liu&Min Hu.(2016).Association of Long Non-Coding RNA HOTAIR Polymorphisms with Cervical Cancer Risk in a Chinese Population.PLOS ONE,11,(7)
MLA:
Liangsheng Guo,et al."Association of Long Non-Coding RNA HOTAIR Polymorphisms with Cervical Cancer Risk in a Chinese Population".PLOS ONE 11..7(2016):e0160039