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Role of RbBP5 and H3K4me3 in the vicinity of Snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell

2016; Impact Journals LLC; Volume: 7; Issue: 40 Linguagem: Inglês

10.18632/oncotarget.11549

1949-2553

Dong Li, Hui Sun, Wenjing Sun, Hongbo Bao, Shuhan Si, Jialin Fan, Ping Lin, Rongjun Cui, Yujia Pan, Simin Wen, Xiulan Zheng, Xiaoguang Yu,

RNA modifications and cancer

// Dong Li 1, * , Hui Sun 1, 3, * , Wen-jing Sun 1 , Hong-bo Bao 4 , Shu-han Si 1 , Jia-lin Fan 1 , Ping Lin 1 , Rong-jun Cui 1, 5 , Yu-jia Pan 1 , Si-min Wen 1 , Xiu-lan Zheng 2, $ , Xiao-guang Yu 1 1 Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China 2 Department of Ultrasonography, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China 3 Department of Clinical Laboratory, The Second Clinical Medical School of Inner Mongolia University for The Nationalities, (Inner Mongolia Forestry General Hospital), Hulunbuir, Inner Mongolia 022150, P.R. China 4 Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China 5 Department of Biochemistry and Molecular Biology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157000, P.R. China * These authors have contributed equally to this work $ Senior author Correspondence to: Xiao-Guang Yu, email: xiaoguang_yu@hotmail.com Keywords: Snail, H3K4me3, RbBP5, EMT, prostate cancer Received: April 13, 2016 Accepted: August 13, 2016 Published: August 23, 2016 ABSTRACT EMT (epithelial- mesenchymal transition) occurs in a wide range of tumor types, and has been shown to be crucial for metastasis. Epigenetic modifications of histones contribute to chromatin structure and result in the alterations in gene expression. Tri-methylation of histone H3 lysine 4 (H3K4me3) is associated with the promoters of actively transcribed genes and can serve as a transcriptional on/off switch. RbBP5 is a component of the COMPASS/ -like complex, which catalyzes H3K4me3 formation. In this study, we found that in the process of TGF-Beta1 induced EMT in the prostate cancer cell line DU145, H3K4me3 enrichment and RbBP5 binding increased in the vicinity of Snail (SNAI1) transcription start site. Knocking-down of RbBP5 notably decreased Snail expression and EMT. Recruitment of RbBP5 and formation of H3K4me3 at Snail TSS during EMT depend on binding of SMAD2/3 and CBP at Snail TSS. This study links the SMAD2/3 signal with Snail transcription via a histone modification - H3K4me3. Furthermore, our research also demonstrates that RbBP5 and even WRAD may be a promising therapeutic candidates in treating prostate cancer metastasis, and that DU145 cells maintain their incomplete mesenchymal state in an auto/ paracrine manner.