2. Academic Validation
  3. Stabilization of SETD3 by deubiquitinase USP27 enhances cell proliferation and hepatocellular carcinoma progression

Stabilization of SETD3 by deubiquitinase USP27 enhances cell proliferation and hepatocellular carcinoma progression

  • Cell Mol Life Sci. 2022 Jan 12;79(1):70. doi: 10.1007/s00018-021-04118-9.
Tingting Zou 1,  Yang Wang 1,  Ling Dong 1 2,  Tiantian Che 1,  Huakan Zhao 3,  Xiaohua Yan 4,  Zhenghong Lin 5
Affiliations

Affiliations

  • 1 School of Life Sciences, Chongqing University, Chongqing, 401331, People's Republic of China.
  • 2 Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yuzhong District, Chongqing, 400016, People's Republic of China.
  • 3 Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China.
  • 4 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China. yanxiaohua@ncu.edu.cn.
  • 5 School of Life Sciences, Chongqing University, Chongqing, 401331, People's Republic of China. zhenghonglin@cqu.edu.cn.
PMID: 35018513 DOI: 10.1007/s00018-021-04118-9
Abstract

The Histone Methyltransferase SETD3 plays critical roles in various biological events, and its dysregulation is often associated with human diseases including Cancer. However, the underlying regulatory mechanism remains elusive. Here, we reported that ubiquitin-specific peptidase 27 (USP27) promotes tumor cell growth by specifically interacting with SETD3, negatively regulating its ubiquitination, and enhancing its stability. Inhibition of USP27 expression led to the downregulation of SETD3 protein level, the blockade of the cell proliferation and tumorigenesis of hepatocellular carcinoma (HCC) cells. In addition, we found that USP27 and SETD3 expression is positively correlated in HCC tissues. Notably, higher expression of USP27 and SETD3 predicts a worse survival in HCC patients. Collectively, these data elucidated that a USP27-dependent mechanism controls SETD3 protein levels and facilitates its oncogenic role in liver tumorigenesis.

Keywords

Cell proliferation; Deubiquitination; Hepatocellular carcinoma; SETD3; USP27.

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