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Histone demethylase RBP2 induced by Helicobactor Pylori CagA participates in the malignant transformation of gastric epithelial cells

2014; Impact Journals LLC; Volume: 5; Issue: 14 Linguagem: Inglês

10.18632/oncotarget.2185

1949-2553

Xiuming Liang, Jiping Zeng, Lixiang Wang, Li Shen, Shuyan Li, Lin Ma, Xinyu Ci, Jingya Yu, Mutian Jia, Yundong Sun, Zhifang Liu, Shili Liu, Wenjuan Li, Han Yu, Chunyan Chen, Jihui Jia,

Cancer-related gene regulation

// Xiuming Liang 1 , Jiping Zeng 2 , Lixiang Wang 3 , Li Shen 1 , Shuyan Li 1 , Lin Ma 1 , Xinyu Ci 1 , Jingya Yu 1 , Mutian Jia 1 , Yundong Sun 1 , Zhifang Liu 2 , Shili Liu 1 , Wenjuan Li 1 , Han Yu 1 , Chunyan Chen 4 and Jihui Jia 1 1 Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China 2 Department of Biochemistry, School of Medicine, Shandong University, Jinan, PR China 3 Department of Pharmacology, School of Medicine, Shandong University, Jinan, PR China 4 Department of Hematology, Qilu Hospital, Shandong University, No.107,Wenhua Xi Road, Jinan 250012, Shandong, P. R. China Correspondence: Jihui Jia, email: // Keywords : RBP2, CagA, GC, Sp1, malignant transformation Received : May 17, 2014 Accepted : July 06, 2014 Published : July 08, 2014 Abstract Gastric epithelial cell malignant transformation induced by Helicobactor Pylori contributes to tumor development, but the underlying mechanisms for this remain unclear. Here we demonstrate that RBP2, a newly identified histone demethylase, can be induced by CagA via PI3K/AKT-Sp1 pathway depending on AKT phosphorylation. Sp1 directly binds to RBP2 promoter and enhances its expression then the upregulated RBP2 significantly increases Cyclin D1 transcription, which contributes to gastric epithelial cell malignant transformation. Further data indicate that knockdown of endogenous RBP2 dominantly inhibits gastric cancer (GC) development both in vitro and in vivo. In conclusion, this CagA- PI3K/AKT-Sp1-RBP2-Cyclin D1 pathway may serve as a novel mechanism for gastric epithelial cell malignant transformation and then gastric cancer (GC). Therefore, RBP2 may link chronic inflammation to tumor development and its inhibition may have potential therapeutic advantages.