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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.
Highlights
Oral squamous cell carcinoma (OSCC) is a type of head and neck cancers and represents around 90% of all malignant neoplasms of the oral cavity [1]
We examined the significance of long non-coding RNAs (lncRNAs) HOTAIR (HOX transcript antisense RNA) in tumor progression of oral squamous cell carcinomas (OSCC)
It has been shown that HOTAIR contributes to chemoresistance through PI3K/AKT/MRP1 [36], wnt/βcatenin [37] pathways or downregualtion of p21 [22] in other carcinomas
Summary
Oral squamous cell carcinoma (OSCC) is a type of head and neck cancers and represents around 90% of all malignant neoplasms of the oral cavity [1]. HOX antisense intergenic RNA (HOTAIR) is one of the well-known oncogenic lncRNAs. It has been demonstrated that HOTAIR was up-regulated in cancer tissues, especially in head and neck squamous cell carcinoma (HNSCC) [15,16,17]. The expression level of HOTAIR was correlated with tumor size and clinical stage in OSCC [19, 24] and HOTAIR has been suggested as a prognosis factor for HNSCC [16, 17, 25]. HOTAIRmediated regulation of oral carcinomas stem cells (OCSC) still remains to be elucidated
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