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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Histone methyltransferase SETDB1 promotes cells proliferation and migration by interacting withTiam1 in hepatocellular carcinoma

Authors: Yuqin Zhang, Jing Huang, Qisheng Li, Keli Chen, Yonghao Liang, Zetao Zhan, Feng Ye, Wen Ni, Longhua Chen, Yi Ding

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

SETDB1 is a histone H3K9 methyltransferase, which plays a significant role in the occurrence and progression of tumors. Previous studies have confirmed that T-lymphom invasion and metastasis gene (Tiam1) is a protein associated with the metastasis of hepatocellular carcinoma (HCC); however, we have not yet been successful in elucidating the specific mechanism of HCC.

Methods

Yeast two-hybrid test was conducted to screen proteins that interacted with Tiam1 gene. Glutathione-S-transferase (GST) pull-down and crosslinking-immunoprecipitation (CLIP) assays were performed to determine whether SETDB1 can interact with Tiam1 gene. A series of related experiments were performed to explore role of SETDB1 on cell proliferation, migration, and invasion in HCC. Recovery experiment was performed to investigate the effect of Tiam1 knockdown on cell proliferation and migration, which was caused by SETDB1 overexpression in HCC cells. The expression of SETDB1 was frequently upregulated in HCC tissues and positively correlated with Tiam1.

Results

GST pull-down and CLIP assays were performed to elucidate the interaction between SETDB1 and Tiam1. Cell proliferation, migration, and epithelial mesenchymal transformation (EMT) in HCC cells was promoted with the overexpression of SETDB1. Following the knockdown of Tiam1 gene, the effect of SETDB1 on cell proliferation and migration was reversed in HCC cells. The expression of SETDB1 was frequently up-regulated in HCC tissues, and it was positively correlated with Tiam1 gene.

Conclusions

Ours is the first study to prove that SETDB1 promotes the proliferation and migration of cells by forming SETDB1-Tiam1 compounds. We found that SETDB1-Tiam1 compounds were involved in a novel pathway, which regulated epigenetic modification of gene expression in HCC samples.
Appendix
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Metadata
Title
Histone methyltransferase SETDB1 promotes cells proliferation and migration by interacting withTiam1 in hepatocellular carcinoma
Authors
Yuqin Zhang
Jing Huang
Qisheng Li
Keli Chen
Yonghao Liang
Zetao Zhan
Feng Ye
Wen Ni
Longhua Chen
Yi Ding
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4464-9

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