KDM4B promotes epithelial-mesenchymal transition through up-regulation of ZEB1 in pancreatic cancer.
Lysine (K)-specific demethylase 4B (KDM4B) is a histone H3K9 demethylase and is reported to activate gene transcription through regulation of chromatin structures. Previous research has revealed that KDM4B plays special regulatory roles in colorectal, prostate and gastric cancers. However, its physiological role in pancreatic cancer remains largely unknown. In the present study, it is demonstrated KDM4B plays a crucial in epithelial-mesenchymal transition (EMT) in pancreatic cancer. siRNA mediated silencing of KDM4B inhibits cell migration, invasion and EMT. Moreover, KDM4B was demonstrated to epigenetically regulate the expression of ZEB1 in the TGF-β-induced EMT process. In tumor tissues of pancreatic cancer patient, the protein level of KDM4B was positively correlated with ZEB1. In conclusion, our results suggested that KDM4B is a key mediator in EMT process, and may serve as an important prognostic marker and therapeutic target for the metastatic progression of human pancreatic cancer.
Department of Intervetional Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Shuo
S
Li
Department of Oncology, Tengzhou Central People's Hospital, Tengzhou 277500, China.
Linlin
L
Wu
Department of Intervetional Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Qingbing
Q
Wang
Cancer Research Institute, Shanghai Cancer Center, Fudan University, Shanghai 200032, China liyingyi@fudan.edu.cn wangxl_shmu@163.com.
Yingyi
Y
Li
Department of Intervetional Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China liyingyi@fudan.edu.cn wangxl_shmu@163.com.
Xiaolin
X
Wang
D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011379:Prognosis; D015854:Up-Regulation; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism*
D014408:Biomarkers, Tumor; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D056484:Jumonji Domain-Containing Histone Demethylases; C523637:KDM4B protein, human
KDM4B; TGF-β; ZEB1; epithelial-mesenchymal transition; pancreatic cancer