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

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.

• Authors: Tingting Zou, Yang Wang, Ling Dong, Tiantian Che, Huakan Zhao, Xiaohua Yan, Zhenghong Lin
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 79 Issue 1 Pg. 70 (Jan 12 2022) ISSN: 1420-9071 [Electronic] Switzerland
• PMID: 35018513 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Histone Methyltransferases
• SETD3 protein, human
• USP27X protein, human
• Ubiquitin-Specific Proteases

Topics

• Carcinoma, Hepatocellular (mortality, pathology)
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Cell Transformation, Neoplastic (pathology)
• Disease Progression
• Gene Expression Regulation, Neoplastic (genetics)
• Gene Knockdown Techniques
• HEK293 Cells
• Histone Methyltransferases (genetics, metabolism)
• Humans
• Liver Neoplasms (mortality, pathology)
• Ubiquitin-Specific Proteases (genetics, metabolism)
• Ubiquitination (physiology)