SET7/9 promotes hepatocellular carcinoma progression through regulation of E2F1

Gu,Ye; Wang,Xinling; Liu,Hong; Li,Guimei; Yu,Weiping; Ma,Qing

doi:10.3892/or.2018.6621

SET7/9 promotes hepatocellular carcinoma progression through regulation of E2F1

Authors:
- Ye Gu
- Xinling Wang
- Hong Liu
- Guimei Li
- Weiping Yu
- Qing Ma
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Affiliations: Department of Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu, 210009, P.R. China, Department of Pathology, No. 81 Hospital of PLA, Nanjing, Jiangsu 210002, P.R. China, Department of Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu, 210009, P.R. China, College of Biological and Environmental Engineering, Zhejiang Shuren University, Hangzhou, Zhejiang 310015, P.R. China
Published online on: August 2, 2018 https://doi.org/10.3892/or.2018.6621
Pages: 1863-1874
Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Histone‑lysine N‑methyltransferase SET7/9 is a protein lysine monomethylase that methylates histone H3K4 as well as various non‑histone proteins. Deregulation of SET7/9 is frequently detected in human cancers. However, the role of SET7/9 in HCC development remains unclear. In the present study, upregulation of SET7/9 and E2F transcription factor 1 (E2F1) expression was detected in 68 samples of HCC tissues compared with these levels noted in the paired healthy liver samples. The expression levels of SET7/9 and E2F1 were significantly correlated with pathological stage and tumor size. Subcellular fractionation and co‑immunoprecipitation analyses revealed protein‑protein interaction between SET7/9 and E2F1 in the cytoplasm of HCC cells. Silencing of SET7/9, as well as treatment with 5'‑deoxy‑5'‑methylthioadenosine (MTA), a protein methylation inhibitor, led to reduced E2F1 protein abundance in HCC cells. Using Cell Counting Kit‑8 (CCK‑8) assay, Transwell migration assay and wound healing assay, significantly decreased cell proliferation, migration and invasion were observed in cells exhibiting downregulation of SET7/9 and E2F1 expression, as well as in wild‑type HCC cells treated with MTA. Furthermore, SET7/9 downregulation and MTA treatment resulted in reduced expression of downstream targets of E2F1, including cyclin A2, cyclin E1 and CDK2. In conclusion, the present study revealed an oncogenic function of SET7/9 in HCC and demonstrated that SET7/9 may be responsible for alterations in the proliferative ability, aggressiveness and invasive/metastatic potential of HCC cells through post‑translational regulation of E2F1.

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