1. Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People's Republic of China
2. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People's Republic of China
3. Otolaryngology Major Disease Research Key Laboratory of Hunan Province, 87 Xiangya Road, Changsha, Hunan 410008, People's Republic of China
Long non-coding RNAs (lncRNAs) are potentially critical regulators of cancer malignant behaviours. Aberrant expression and dysfunction of lncRNA PVT1 have been reported in multiple human cancers. However, its role in squamous cell carcinoma of the head and neck (SCCHN) remains largely unknown. Our current study demonstrated that PVT1 expression was increased in SCCHN. High PVT1 expression was positively correlated with SCCHN clinical parameters including T classification, clinical stages and cervical lymph node metastasis. More importantly, high PVT1 expression predicted a poor prognosis in SCCHN patients. Gain-of function and loss-of function studies further indicated that PVT1 promoted the proliferation and invasion of SCCHN both in vitro and in vivo, which was accompanied by epithelial-mesenchymal transition and enhanced cancer stem cell-like properties. Further mechanistic investigation revealed that PVT1 activated Wnt/β-catenin signalling pathway, and inhibition of Wnt/β-catenin signalling reversed the malignant progression caused by PVT1 overexpression. Together, our study reveals that PVT1 accelerates the malignant progression of SCCHN and represents a potential biomarker and therapeutic target in SCCHN.
Keywords: Squamous cell carcinoma of the head and neck, Plasmacytoma variant translocation 1, metastasis, epithelial-mesenchymal transition, stemness, Wnt/β-catenin