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.

Ge XS ，Ma HJ ，Zheng XH ，Ruan HL ，Liao XY ，Xue WQ ，Chen YB ，Zhang Y ，Jia WH ... -  《-》

Long non-coding RNA HOTAIR, a driver of malignancy, predicts negative prognosis and exhibits oncogenic activity in oesophageal squamous cell carcinoma.

Li X ，Wu Z ，Mei Q ，Li X ，Guo M ，Fu X ，Han W ... -  《-》

lncRNA UCA1 inhibits esophageal squamous-cell carcinoma growth by regulating the Wnt signaling pathway.

Wang X ，Gao Z ，Liao J ，Shang M ，Li X ，Yin L ，Pu Y ，Liu R ... -  《journal of toxicology and environmental health》

Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis.

Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern of the lncRNA HOTAIR and assess its biological role in the development and progression of esophageal squamous cell carcinoma (ESCC), HOTAIR expression in ESCC tissues and adjacent noncancerous tissues were collected from 78 patients and measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). HOTAIR correlation with clinicopathological features and prognosis was also analyzed. Suppression of HOTAIR using siRNA treatment was performed in order to explore its role in tumor progression. Notably elevated HOTAIR expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (96%, P < 0.01), showing a high correlation with cancer metastasis (P < 0.01), elevated TNM (2009) stage classification (P < 0.01), and lowered overall survival rates (P = 0.003). Multivariate analysis revealed that HOTAIR expression (P = 0.003) is also an independent prognostic factor for comparison of TNM stage (P = 0.024) and lymph node metastasis (P = 0.010). Furthermore, in vitro assays of the ESCC cell line KYSE30 demonstrated that knockdown of HOTAIR reduced cell invasiveness and migration while increasing the response of cells to apoptosis. Thus, HOTAIR is a novel molecule involved in both ESCC progression and prognosis. Full elucidation of HOTAIR functionality relevant to ESCC may open avenues for the use of lncRNAs in identification of novel drug targets and therapies for ESCC and other prevalent cancers.

Chen FJ ，Sun M ，Li SQ ，Wu QQ ，Ji L ，Liu ZL ，Zhou GZ ，Cao G ，Jin L ，Xie HW ，Wang CM ，Lv J ，De W ，Wu M ，Cao XF ... -  《-》

A long non-coding RNA, HOTAIR, promotes cartilage degradation in osteoarthritis by inhibiting WIF-1 expression and activating Wnt pathway.

Yang Y ，Xing D ，Wang Y ，Jia H ，Li B ，Li JJ ... -  《BMC Molecular and Cell Biology》