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

Ming Yi Lu, Yi Wen Liao, Pei Yin Chen, Pei Ling Hsieh, Chih Yuan Fang, Chia Yu Wu, Ming Liang Yen, Bou Yue Peng, Dayen Peter Wang, Hsin Chung Cheng, Ching Zong Wu, Yung Hsun Shih, Duen Jeng Wang, Cheng Chia Yu, Lo Lin Tsai

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)98542-98552
Number of pages11
JournalOncotarget
Volume8
Issue number58
DOIs
Publication statusPublished - Jan 1 2017

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Keywords

  • Cancer stem cells
  • HOTAIR
  • Long non-coding RNA
  • Mesenchymal
  • Oral squamous cell carcinomas

ASJC Scopus subject areas

  • Oncology

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