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The downregulation of ANGPTL4 inhibits the migration and proliferation of tongue squamous cell carcinoma
Institution:1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China;2. Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China;3. Department of Stomatology, the 12th Guangzhou People’s Hospital, Guangzhou, Guangdong, 510620, China;4. Department of Prosthodontics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China;1. Department of Clinical Lab, Weihai Municipal Hospital, Dalian Medical University, Weihai, Shandong, China;2. College of Medical Laboratory of Dalian Medical University, Dalian, Liaoning, China;1. Department of Clinical Laboratory of South Building, Chinese PLA General Hospital, Beijing, China;2. First Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China;3. Department of Respiratory Disease of South Building, Chinese PLA General Hospital, Beijing, China;4. Second Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China;5. Pharmacy Department, Hospital of Chinese Peoples Armed Police Forces, Beijing 100039, PR China;1. Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre 91501970, Brazil;2. Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501970, Brazil;1. Glasgow University, Dental School, United Kingdom;2. Glasgow University, MVLS College, Dental School, University of Glasgow, United Kingdom;3. University of Hong Kong, Hong Kong;4. University Hospital Crosshouse, Kilmarnock, United Kingdom;1. Taibah University Dental College, Almadinah, Saudi Arabia;2. Preventive Dental Science, Taibah University Dental College & Hospital, Almadinah, Saudi Arabia;3. Oral and Maxillofacial Surgery, Taibah University Dental College & Hospital, Almadinah, Saudi Arabia
Abstract:ObjectiveTongue squamous cell carcinoma (TSCC) is the most common malignant cancer in the oral cavity, with a high rate of metastasis to the neck lymphoid node. Angiopoietin-like protein 4 (ANGPTL4) and microvessel density (MVD) may be novel indicators for tumor metastasis. The aim of the present study was to investigate the expression and function of ANGPTL4 in TSCC and the relationship between ANGPTL4 and MVD.MethodsThe expression levels of ANGPTL4 and MVD (CD34) were analyzed in 65 TSCC specimens and the adjacent non-cancerous tissues using immunohistochemistry (IHC). siRNA was delivered into TSCCA cells to downregulate ANGPTL4 expression. Subsequently, validation with real-time RT-PCR and western blot analyses was performed to analyze ANGPTL4 expression levels. In addition, a proliferation assay, migration and invasion assays were carried out.ResultsANGPTL4 expression was associated with tumor stage, lymph node metastasis and MVD expression. Cox regression analysis showed that high levels of ANGPTL4 expression were closely associated with poor survival time. In vitro analyses using qRT-PCR and western blot confirmed that ANGPTL4 was successfully inhibited in TSCCA cells. Suppressing ANGPTL4 resulted in the inhibition of cell proliferation and migration, but neither invasion nor cisplatin resistance was significantly affected.ConclusionHigh expression levels of ANGPTL4 are associated with the T stage, lymphatic metastasis, angiogenesis and poor overall survival in TSCC patients. The downregulation of ANGPTL4 inhibits the migration and proliferation of cells in TSCC. Taken together, ANGPTL4 may serve as a novel biomarker and therapeutic target for TSCC.
Keywords:Tongue squamous cell carcinoma  ANGPTL4  Microvessel density  Proliferation  Migration  Invasion
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