title: KDM6B Elicits Cell Apoptosis by Promoting Nuclear Translocation of FOXO1 in Non-Small Cell Lung Cancer.
abstract: OBJECTIVE
  Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer and the cause of most cancer-related deaths. The molecular mechanisms that are involved in NSCLC development are currently not well understood. Accumulating evidence shows that histone demethylases play important roles in the regulation of pathological developmental processes in many diseases, including various types of cancers.
  
  
  METHODS
  Mitochondrial membrane potential assays, migration and invasion assays, caspase-3 and caspase-9 activity assays and western blot analysis were used in this research.
  
  
  RESULTS
  We found that overexpression of KDM6B, a demethylase that acts on histone H3 at lysine 27 (H3K27), inhibited cell growth by initiating mitochondria-dependent apoptosis and by attenuating the invasion-metastasis cascade in NSCLC cells. Moreover, our results showed that KDM6B directly interacted with FOXO1 and that overexpression of KDM6B promoted nuclear accumulation of FOXO1. The effects of KDM6B on cell apoptosis and metastasis were weakened by knockdown of FOXO1 expression. On the contrary, knocking down expression of KDM6B inhibited cell apoptosis and promoted cell growth by mitigating the nuclear translocation of FOXO1 in NSCLC cells.
  
  
  CONCLUSIONS
  These findings suggest that KDM6B may act in a pro-apoptotic role in NSCLC by causing the nuclear translocation of FOXO1.
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Jun
authors: J
authors: Ma
authors: Ning
authors: N
authors: Wang
authors: Yurong
authors: Y
authors: Zhang
authors: Cun
authors: C
authors: Wang
authors: Tianxiang
authors: T
authors: Ge
authors: Haojie
authors: H
authors: Jin
authors: Xuan
authors: X
authors: Deng
authors: Xisong
authors: X
authors: Huo
authors: Dishui
authors: D
authors: Gu
authors: Zhouhong
authors: Z
authors: Ge
authors: Wei
authors: W
authors: Chu
authors: Liyan
authors: L
authors: Jiang
authors: Wenxin
authors: W
authors: Qin
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000235:genetics / Q000502:physiology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006657:Histones; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; D053148:Caspase 3; D053453:Caspase 9