Targeting LncRNA HOTAIR suppresses cancer stemness and metastasis in oral carcinomas stem cells through modulation of EMT.

// Ming-Yi Lu 1, 2, * , Yi-Wen Liao 1, * , Pei-Yin Chen 1, 2 , Pei-Ling Hsieh 3 , Chih-Yuan Fang 4, 5 , Chia-Yu Wu 5, 6 , Ming-Liang Yen 6 , Bou-Yue Peng 5, 6 , Dayen Peter Wang 5, 6 , Hsin-Chung Cheng 5, 6 , Ching-Zong Wu 5, 6 , Yung-Hsun Shih 4, 6 , Duen-Jeng Wang 6 , Cheng-Chia Yu 1, 2, 3 and Lo-Lin Tsai 4, 6 1 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 4 Department of Dentistry, Taipei Municipal Wanfang Hospital, Taipei, Taiwan 5 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 6 Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Cheng-Chia Yu, email: ccyu@csmu.edu.tw Lo-Lin Tsai, email: lolintsai@tmu.edu.tw Keywords: oral squamous cell carcinomas; long non-coding RNA; HOTAIR; cancer stem cells; mesenchymal Received: May 16, 2017     Accepted: August 26, 2017     Published: October 07, 2017 ABSTRACT Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, such as cell growth, apoptosis and tumorigenesis. However, the functional roles of lncRNAs and mechanistic analysis of their interplays with oncogenic pathways in oral cancer remain largely unknown. In the current study, we examined the significance of lncRNA HOTAIR (HOX transcript antisense RNA) in tumor progression of oral squamous cell carcinomas (OSCC). We found the expression of HOTAIR was upregulated in tumor tissues, especially in the metastatic samples. And it was also observed in metastatic OSCC cell lines. Silence of HOTAIR in oral carcinomas stem cells (OCSC) significantly inhibited their cancer stemness, invasiveness and tumourigenicity in xenotransplantation models. By contrast, overexpression of HOTAIR in OSCC enhanced their metastatic potential and epithelial-mesenchymal transition (EMT) characteristics. And we showed that the expression of HOTAIR was positively related to mesenchymal markers and inversely correlated with epithelial marker in clinical samples. Moreover, Kaplan-Meier survival analysis suggested that high level of HOTAIR was a strong predictor of poor survival in OSCC patients. Collectively, our data demonstrated that HOTAIR-mediated cancer stemness and metastasis are associated with the regulation of EMT and HOTAIR may serve as a therapeutic target in OSCC.