2. Academic Validation
  3. The deubiquitinating enzyme USP19 facilitates hepatocellular carcinoma progression through stabilizing YAP

The deubiquitinating enzyme USP19 facilitates hepatocellular carcinoma progression through stabilizing YAP

  • Cancer Lett. 2023 Oct 11:216439. doi: 10.1016/j.canlet.2023.216439.
Zelin Tian 1,  Chen Xu 1,  Weixiang He 2,  Zhibin Lin 1,  Wenjie Zhang 3,  Kaishan Tao 1,  Rui Ding 1,  Xuan Zhang 4,  Kefeng Dou 5
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.
  • 2 Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China.
  • 3 Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China; Chinese Education Ministry's Key Laboratory of Western Resources and Modern Biotechnology, Key Laboratory of Biotechnology Shaanxi Province, College of Life Sciences, Northwest University, Xi'an, China.
  • 4 Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China. Electronic address: zhangxuantj@163.com.
  • 5 Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China. Electronic address: doukef@fmmu.edu.cn.
PMID: 37832781 DOI: 10.1016/j.canlet.2023.216439
Abstract

Hippo pathway plays a crucial role in the progression of hepatocellular carcinoma (HCC), and yes-associated protein (YAP) is one of the major factors of the Hippo pathway. However, the mechanism of abnormal YAP activation in HCC has not been well elucidated. Here, we screened a Deubiquitinating enzymes' (DUB) siRNA library targeting DUBs, and identified Ubiquitin Specific Peptidase 19 (USP19) as a specific deubiquitinating Enzyme of YAP in HCC, which could stabilize YAP at K76 and K90 sites via removing the K48- and K11-linked ubiquitin chains. USP19 knockdown decreased the expression of YAP protein and its target gene (CTGF, CYR61, ANKRD1) expression. Through substantial in vivo and in vitro experiments, we prove that USP19 facilities the proliferation and migration of HCC. More importantly, we found that USP19 was upregulated in HCC tissues and associated with poor prognosis. In general, our research revealed a novel post-translational mechanism between USP19 and YAP in HCC, suggesting that USP19 may be a pivotal therapeutic target for HCC treatment.

Keywords

Deubiquitination; HCC; Hippo pathway; USP19.

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