title: HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway.
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.
authors.affiliation: Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: Ge
authors.forename: Hua-Juan
authors.initials: HJ
authors.lastname: Ma
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zheng
authors.forename: Hong-Lian
authors.initials: HL
authors.lastname: Ruan
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liao
authors.forename: Wen-Qiong
authors.initials: WQ
authors.lastname: Xue
authors.forename: Yuan-Bin
authors.initials: YB
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D054387:Receptors, CXCR / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C501896:ACKR3 protein, human; D048868:Adaptor Proteins, Signal Transducing; C486356:FGF12 protein, human; C484579:FOXQ1 protein, human; D051858:Forkhead Transcription Factors; C561566:HOTAIR long untranslated RNA, human; D006657:Histones; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D054387:Receptors, CXCR; D012097:Repressor Proteins; C485569:WIF1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D005346:Fibroblast Growth Factors