title: Identification of TDP-43 as an oncogene in melanoma and its function during melanoma pathogenesis.
abstract: Although recent studies have revealed TAR (trans-activating response region) DNA binding protein (TDP-43) as a potential therapeutic target for cancers, its role and clinical association with melanoma have not been explored.
  
  
  
  To identify the role and function of TDP-43 during melanoma pathogenesis.
  
  
  
  Firstly, the relationship between TDP-43 expression and patient survival was explored. Then TDP-43 expression level in melanoma tissue and different melanoma cell lines was measured. After silencing TDP-43 expression in melanoma cells, the impacts of TDP-43 on cellular proliferation, metastasis, glucose uptake, and glucose transporters levels were studied. In the end, effect of TDP-43 depletion on tumorigenicity of melanoma cells was tested in vivo.
  
  
  
  Our results showed that TDP-43 was overexpressed in melanoma paraffin samples compared with that in nevi tissues. The high expression level of TDP-43 was associated with poor patient survival. By silencing TDP-43, we saw significant inhibition of cell proliferation and metastasis in A375 and WM451 cells. TDP-43 knockdown could suppress glucose transporter type-4 (GLUT4) expression and reduce glucose uptake. And downregulation of GLUT4 in melanoma cells induced inhibition of cell proliferation and metastasis. TDP-43 knockdown significantly slowed down tumor growth and decreased GLUT4 expression in vivo.
  
  
  
  TDP-43 is a novel oncogene in melanoma and regulates melanoma proliferation and metastasis potentially through modulation of glucose metabolism.
authors: a Department of Plastic and Reconstructive Surgery , Third Xiangya Hospital of Central South University , Changsha , China.|b Department of Dermatology , Third Xiangya Hospital of Central South University , Changsha , China.
authors: Qinghai
authors: Q
authors: Zeng
authors: c Department of Oncology , Third Xiangya Hospital of Central South University , Changsha , China.
authors: Ke
authors: K
authors: Cao
authors: a Department of Plastic and Reconstructive Surgery , Third Xiangya Hospital of Central South University , Changsha , China.
authors: Rui
authors: R
authors: Liu
authors: b Department of Dermatology , Third Xiangya Hospital of Central South University , Changsha , China.
authors: Jinhua
authors: J
authors: Huang
authors: d State Key Laboratory of Medical Genetics, Central South University , Changsha , China.
authors: Kun
authors: K
authors: Xia
authors: e Institute of Medical Physics and Engineering , Department of Engineering Physics, Tsinghua University , Beijing , China.
authors: Jintian
authors: J
authors: Tang
authors: f Department of Dermatology , Xiangya Hospital of Central South University , Changsha , China.
authors: Xiang
authors: X
authors: Chen
authors: g Cancer Research Institute, Key Laboratory of Carcinogenesis of Ministry of Health, Central South University , Changsha , China.
authors: Ming
authors: M
authors: Zhou
authors: h Department of Rehabilitation , Third Xiangya Hospital of Central South University , Changsha , China.
authors: Huiqing
authors: H
authors: Xie
authors: a Department of Plastic and Reconstructive Surgery , Third Xiangya Hospital of Central South University , Changsha , China.
authors: Jianda
authors: J
authors: Zhou
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009857:Oncogenes; D011379:Prognosis; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; C495692:SLC2A4 protein, human; C000598624:TARDBP protein, human
keywords: GLUT4; TDP-43; glucose metabolism; melanoma; metastasis; proliferation