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

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. HOTAIR, a long non coding RNA, has been linked to the progression of several types of human cancer. In this study, we found that HOTAIR was not only significantly up‐regulated in tumor tissues, but also significantly associated with poor clinical outcome in patients with esophageal squamous cell carcinoma (ESCC). ESCC cells with HOTAIR overexpression displayed aberrant activated WNT signaling pathway by inhibiting the expression of WNT‐inhibitor factor 1, thereby promote the migration and invasion of ESCC cells. On the contrary, silencing of HOTAIR in ESCC cells led to decreased migration and invasion ability. Together, these results suggest that HOTAIR overexpression may serve as a novel prognostic biomarker and potential therapeutic target for the treatment of human ESCC.