title: Ovol2 gene inhibits the Epithelial-to-Mesenchymal Transition in lung adenocarcinoma by transcriptionally repressing Twist1.
abstract: BACKGROUND
  Associated with recent achievements in therapy for advanced lung adenocarcinoma, there will still be an unmet medical need for effective treatment of stage IIIb/IV, and the prognosis of lung cancer is not optimistic till now.
  
  
  OBJECTIVE
  In order to obtain some essential evidences for a potential targeted therapy in lung adenocarcinoma, the effects of Ovol2 gene on Epithelial-to-Mesenchymal Transition (EMT) was observed and the probable mechanisms were analyzed.
  
  
  METHODS
  Ovol2 expression was previously evaluated by immunochemistry in lung adenocarcinoma tissue, and Ovol2 was overexpressed by lentivirus infection in A549 cells. Subsequently, the migration and invasion ability of A549 cells was tested by Transwell and Wound healing experiments. The mRNA level of genes correlated to EMT was detected by Real-time PCR, and the expression of reasonable makers was probed by Western Blot. Finally, rescue experiment, Luciferase assay, and chromatin immunoprecipitation assay were performed to explore the probable mechanisms.
  
  
  RESULTS
  After treated with Ovol2 overexpression, the expression level of E-cadherin was increased, while the expression level of Vimentin and Twist1 was declined not only in the mRNA level but also in the protein level. Moreover, we found that Ovol2 represses transcription of Twist1 by binding to its promoter directly. Wound healing and Transwell assays indicate that the migration and invasion ability were downregulated by Ovol2 in A549 cells.
  
  
  CONCLUSIONS
  Ovol2 can suppress migration and invasion ability of A549 cells, and prevent EMT by inhibition of Twist1 transcription directly.
authors.affiliation: PLA 174th Clinical College of Anhui Medical University, China.
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: PLA 174th Clinical College of Anhui Medical University, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of cardiothoracic Surgery, PLA 174th Hospital, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of cardiothoracic Surgery, PLA 174th Hospital, China.
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, China.
authors.forename: Rong-Si
authors.initials: RS
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, China. Electronic address: bali@xmu.edu.cn.
authors.forename: Bo-An
authors.initials: BA
authors.lastname: Li
authors.affiliation: Department of cardiothoracic Surgery, PLA 174th Hospital, China. Electronic address: 13358378777@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Guo
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000235:genetics; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D009687:Nuclear Proteins; C544941:Ovol2 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1
keywords: EMT; Lung adenocarcinoma; Ovol2; Twist1