title: Histone demethylase RBP2 induced by Helicobactor Pylori CagA participates in the malignant transformation of gastric epithelial cells.
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.
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Biochemistry, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Ci
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Mutian
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Yundong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biochemistry, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Shili
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, No.107,Wenhua Xi Road, Jinan 250012, Shandong, P. R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Jia
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism*; D064593:Heterografts; D056466:Histone Demethylases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation; D054840:Retinol-Binding Proteins, Cellular / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C518459:RBP2 protein, human; D054840:Retinol-Binding Proteins, Cellular; C080866:cagA protein, Helicobacter pylori; D056466:Histone Demethylases