UHRF2 decreases H3K9ac expression by interacting with it through the PHD and SRA/YDG domain in HepG2 hepatocellular carcinoma cells

Zhang,Ting; Zhao,Linglin; Zeng,Shengyuan; Bai,Lu; Chen,Junxia; Zhang,Zheng; Wang,Yalan; Duan,Changzhu

doi:10.3892/ijmm.2016.2805

UHRF2 decreases H3K9ac expression by interacting with it through the PHD and SRA/YDG domain in HepG2 hepatocellular carcinoma cells

Authors:
- Ting Zhang
- Linglin Zhao
- Shengyuan Zeng
- Lu Bai
- Junxia Chen
- Zheng Zhang
- Yalan Wang
- Changzhu Duan
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Affiliations: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: November 17, 2016 https://doi.org/10.3892/ijmm.2016.2805
Pages: 126-134
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) is a multi-domain E3 ubiquitin ligase which is involved in epigenetic regulation and plays an essential role in tumorigenesis. However, the role of UHRF2 in histone H3 acetylation has not yet been fully elucidated and few studies have reported its role in hepatocellular carcinoma (HCC). In this study, we examined the correlation between UHRF2 and acetylated H3 in HCC. Immunohistochemistry and western blot analysis demonstrated that the levels of histone H3 lysine 9 acetylation (H3K9ac) and histone H3 lysine 14 acetylation (H3K14ac) were higher in the HCC tissues and HepG2 HCC cells compared with the adjacent non-tumor tissues and L02 normal cells. The level of UHRF2 was higher in the HCC tissues compared with the adjacent non-tumor tissues, but its expression did not exhibit a significant difference between the HepG2 HCC cells and the L02 normal cells. In addition, when comparing the HCC tissues, a higher expression of UHRF2 correlated with a lower expression of H3K9ac in the HCC tissues. The overexpression of UHRF2 increased the expression of H3K9ac in L02 normal cells (P<0.01), but decreased the expression of H3K9ac in HepG2 cancer cells (P<0.05). Moreover, immunofluorescence staining and co-immunoprecipitation assay indicated that UHRF2 co-localized and interacted with H3K9ac in L02 and HepG2 cells and the plant homeodomain (PHD) finger domain was the key domain for UHRF2 directly binding to H3K9ac. Taken together, these results suggest that UHRF2 decreases the expression of H3K9ac in HepG2 HCC cells and interacts with it through the PHD domain.

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