title: Krüppel-like factor 5 promotes lung tumorigenesis through upregulation of Sox4.
abstract: BACKGROUND
  Krüppel-like factor 5 (KLF5), a member of zinc finger class of DNA-binding transcriptional regulators, has attracted attention because of its important regulatory activities linked to diverse functions such as cell growth, proliferation, differentiation, apoptosis and tumorigenesis in a number of systems. However, its biological functions in the initiation and progression of lung tumorigenesis remain largely unexplored.
  
  
  METHODS
  Quantitative realtime PCR and Western Blot were used to detect the expression of KLF5 in lung cancer tissues and cell lines. Retro-viruses were used to generate KLF5 stable expression lung cancer cell line. Small interfering RNA was used to silence the expression of KLF5 and Sox4. BrdU assay was used to determine the proliferation of cells. Luciferase and Chromatin immunoprecipitation assays were used to detect the regulation of Sox4 by KLF5.
  
  
  RESULTS
  KLF5 was up-regulated in lung cancer tissues and cell lines. Overexpression of KLF5 promotes while knockdown of its expression inhibits cell proliferation in two cell lines derived from lung carcinoma. At the molecular level, our results revealed that KLF5 positively regulates Sox4 expression through a transcriptional mechanism. Sox4 deficiency blocked the proliferative roles of KLF5 in lung cancer cells.
  
  
  CONCLUSIONS
  our data identified the KLF5/Sox4 regulatory signaling play an important role in lung tumorigenesis, which might represent novel therapeutic targets to manage lung carcinoma.
authors.affiliation: Department of Oncology, Shanghai First People's Hospital Affiliated Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Zhao
authors.initials: Z
authors.lastname: Dong
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.forename: Xun
authors.initials: X
authors.lastname: Cai
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Wang
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors