School of Life Sciences, Chongqing University, Chongqing, 401331, People's Republic of China.
Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yuzhong District, Chongqing, 400016, People's Republic of China.
Cell Mol Life Sci. 2022 Jan 12;79(1):70. doi: 10.1007/s00018-021-04118-9.
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.
组蛋白甲基转移酶 SETD3 在各种生物事件中发挥着关键作用，其失调通常与包括癌症在内的人类疾病有关。然而，其潜在的调节机制仍不清楚。在这里，我们报道了泛素特异性肽酶 27（USP27）通过与 SETD3 特异性相互作用，负调控其泛素化，增强其稳定性，从而促进肿瘤细胞生长。抑制 USP27 的表达导致 SETD3 蛋白水平下调，阻断肝癌（HCC）细胞的增殖和致瘤性。此外，我们发现 USP27 和 SETD3 的表达在 HCC 组织中呈正相关。值得注意的是，USP27 和 SETD3 的高表达预示着 HCC 患者的生存预后更差。综上所述，这些数据阐明了一个 USP27 依赖性机制控制 SETD3 蛋白水平，并促进其在肝肿瘤发生中的致癌作用。
