HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway
HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway
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DOI：
10.1111/cas.12296
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发表时间：
2013-12-01
期刊：
影响因子：
5.7
通讯作者：
Jia, Wei-Hua
中科院分区：
文献类型：
--
作者：
Ge, Xiao-Song;Ma, Hua-Juan;Jia, Wei-Hua
最近发现长链非编码RNA（LncRNA）在基因组中广泛转录，并且是表观基因组的关键调节因子。HOTAIR作为一种已知的LncRNA，在多种肿瘤中发挥重要作用。本文着重探讨HOTAIR在食管鳞癌中的临床应用价值和生物学功能。结果发现，与其邻近的正常食管组织相比，ESCC中HOTAIR的表达显著上调。同时，HOTAIR高表达患者的预后明显差于低表达患者。此外，HOTAIR在体外被进一步验证为促进ESCC细胞的迁移和侵袭。然后利用基因芯片和定量真实的时间-聚合酶链反应（qPCR）对HOTAIR过表达后的一些有重要意义的特异性分子进行了研究。筛选出在Wnt/beta-catenin信号通路中起重要作用的WIF-1，并通过免疫组化进一步检测。一般而言，HOTAIR和WIF-1表达之间的负相关性在ESCC细胞和组织中均得到证实。HOTAIR通过促进其启动子区域的组蛋白H3 K27甲基化直接降低WIF-1表达，然后激活Wnt/β-catenin信号通路。新发现的HOTAIR /WIF-1轴阐明了ESCC细胞转移的分子机制，并代表了ESCC患者的新治疗靶点。
Long non-coding RNAs (LncRNAs) have been recently found to be pervasively transcribed in the genome and critical regulators of the epigenome. HOTAIR, as a well-known LncRNA, has been found to play important roles in several tumors. Herein, the clinical application value and biological functions of HOTAIR were focused and explored in esophageal squamous cell carcinoma (ESCC). It was found that there was a great upregulation of HOTAIR in ESCC compared to their adjacent normal esophageal tissues. Meanwhile, patients with high HOTAIR expression have a significantly poorer prognosis than those with low expression. Moreover, HOTAIR was further validated to promote migration and invasion of ESCC cells in vitro. Then some specific molecules with great significance were investigated after HOTAIR overexpression using microarray and quantitative real time-polymerase chain reaction (qPCR). WIF-1 playing an important role in Wnt/beta-catenin signaling pathway was selected and further tested by immunehistochemistry. Generally, inverse correlation between HOTAIR and WIF-1 expression was demonstrated both in ESCC cells and tissues. Mechanistically, HOTAIR directly decreased WIF-1 expression by promoting its histone H3K27 methylation in the promoter region and then activated the Wnt/beta-catenin signaling pathway. This newly identified HOTAIR /WIF-1 axis clarified the molecular mechanism of ESCC cell metastasis and represented a novel therapeutic target in patients with ESCC.