• Open Access

HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway

Authors

  • Xiao-Song Ge,

    1. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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    • These authors contributed equally to this work.

  • Hua-Juan Ma,

    1. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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    • These authors contributed equally to this work.

  • Xiao-Hui Zheng,

    1. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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    • These authors contributed equally to this work.

  • Hong-Lian Ruan,

    1. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Xiao-Yu Liao,

    1. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Wen-Qiong Xue,

    1. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Yuan-Bin Chen,

    1. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Ying Zhang,

    1. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Wei-Hua Jia

    Corresponding author
    1. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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Abstract

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/β-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/β-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.

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