title: Jumonji domain containing 2C promotes cell migration and invasion through modulating CUL4A expression in lung cancer.
abstract: Jumonji domain containing 2C (JMJD2C), also named as KDM4C, was found to a transcriptional cofactor and enzyme that catalyzes demethylation of histone H3 lysine 9 and 36. Here in this study, we found that the expression of JMJD2C increased in a majority of the human lung cancer tissues examined compared with adjacent tissues. Furthermore, the expression of JMJD2C was found to be higher in metastatic lung cancer tissues than which in non-metastatic lung cancer tissues. Knockdown of JMJD2C inhibited the ability of migration and invasion of lung cancer cells. Moreover, JMJD2C knockdown was proven to inhibit the tumor hepatic metastasis of lung cancer cells in vivo and epithelial-mesenchymal transition (EMT) in vitro. On the contrary, over-expression of JMJD2C was found to promote the ability of migration, invasion and EMT. As to mechanism, knockdown of JMJD2C was found to inhibit the expression of CUL4A while to promote the expression of p53 and p27. Furthermore, we found that JMJD2C regulated the activities of lung cancer cells by directly controlling the expression of CUL4A in JMJD2C over-expression cell line, and interference of CUL4A was found to reverse the ability of migration, invasion and EMT which JMJD2C over-expression bought to. Together, these results of this study not only enriched the JMJD2C biological function of lung cancer, but also illuminated exploring the prevention and treatment of the invasion and metastasis of lung cancer.
authors.affiliation: Department of Respiratory Medicine Linyi People's Hospital, Linyi, Shandong 276003, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Linyi People's Hospital, Linyi, Shandong 276003, PR China. Electronic address: dazhijiangly@126.com.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Jiang
mesh_terms: D000072283:A549 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D044842:Cullin Proteins / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology*
chemical_list: C114234:CUL4A protein, human; D044842:Cullin Proteins; C413655:KDM4C protein, human; D056484:Jumonji Domain-Containing Histone Demethylases
keywords: CUL4A; Epithelial-mesenchymal transitions; JMJD2C; Lung cancer