Association of Long Non-Coding RNA HOTAIR Polymorphisms with Cervical Cancer Risk in a Chinese Population.
Association of Long Non-Coding RNA HOTAIR Polymorphisms with Cervical Cancer Risk in a Chinese Population.
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DOI：
10.1371/journal.pone.0160039
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hu M
中科院分区：
文献类型：
--
作者：
Guo L;Lu X;Zheng L;Liu X;Hu M
HOTAIR是一种长非编码RNA(LncRNAs)，已被报道在宫颈癌的发生发展过程中上调。然而，LncRNAs中的单核苷酸多态(SNPs)及其与宫颈癌易感性的关系尚未见报道。在目前的研究中，我们假设IncRNA HOTAIR中的SNP可能影响宫颈癌的风险。我们进行了一项病例对照研究，包括510名宫颈癌患者(病例)和713名非癌症个体(对照组)，以探讨LncRNA HOTAIR中三个单倍型标记SNPs(rs920778、rs1899663和rs4759314)与宫颈癌风险的关系。我们发现HOTAIR内含子增强子中的单核苷酸多态rs920778与宫颈癌(P<；10−4)有很强的相关性。此外，TT型纯合子的宫颈癌患者与肿瘤转移(TNM)分期显著相关。体外分析表明，与含有rs920778C等位基因的报告构建体相比，携带rs920778T等位基因的报告构建体具有更高的报告基因转录活性。此外，HOTAIR在宫颈癌组织中的表达高于相应的正常组织，并且这种高表达与风险相关等位基因T有关。综上所述，我们的研究为功能性SNP rs920778调节HOTAIR表达提供了强有力的功能证据，并可能最终影响宫颈癌的易感性。
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.