title: The downregulation of ANGPTL4 inhibits the migration and proliferation of tongue squamous cell carcinoma.
abstract: OBJECTIVE
  Tongue 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  ANGPTL4 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.
  
  
  CONCLUSIONS
  High 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.
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China; Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China. Electronic address: zhiquanhuang1978@126.com.
authors: Zhiquan
authors: Z
authors: Huang
authors: Department of Stomatology, the 12th Guangzhou People's Hospital, Guangzhou, Guangdong, 510620, China. Electronic address: 1693286903@qq.com.
authors: Jiemin
authors: J
authors: Xie
authors: Department of Prosthodontics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China. Electronic address: kaedesd@163.com.
authors: Shiyao
authors: S
authors: Lin
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China; Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China. Electronic address: 635651180@qq.com.
authors: Shihao
authors: S
authors: Li
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China; Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China. Electronic address: zeahuang@hotmail.com.
authors: Zixian
authors: Z
authors: Huang
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China; Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China. Electronic address: sumswangyy@163.com.
authors: Youyuan
authors: Y
authors: Wang
authors: Department of Prosthodontics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China. Electronic address: dutaoye@163.com.
authors: Jiantao
authors: J
authors: Ye
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D055806:Microvessels; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012313:RNA / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D014408:Biomarkers, Tumor; D012313:RNA; D002945:Cisplatin
keywords: ANGPTL4; Invasion; Microvessel density; Migration; Proliferation; Tongue squamous cell carcinoma