Ubiquitin-specific protease 1 acts as an oncogene and promotes lenvatinib efficacy in hepatocellular carcinoma by stabilizing c-kit

Chen, Zhangbin; Ma, Yihui; Guo, Zhitang; Song, Dingyuan; Chen, Zili; Sun, Min

doi:10.1016/j.aohep.2022.100669

Cited by 11 publications

(4 citation statements)

References 25 publications

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“…Different ubiquitin modifications of proteins elicit specific responses depending on the ubiquitinated substrates. In addition, ubiquitinated substrates can act as novel signaling molecules 9 – 11 . Conjugation of ubiquitin to substrate proteins leads to proteasomal degradation and can be reversed by deubiquitinating enzymes 12 .…”

Section: Introductionmentioning

confidence: 99%

Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

et al. 2023

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Nonalcoholic fatty liver disease (NAFLD) occurs due to the accumulation of fat in the liver, leading to fatal liver diseases such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Elucidation of the molecular mechanisms underlying NAFLD is critical for its prevention and therapy. Here, we observed that deubiquitinase USP15 expression was upregulated in the livers of mice fed a high-fat diet (HFD) and liver biopsies of patients with NAFLD or NASH. USP15 interacts with lipid-accumulating proteins such as FABPs and perilipins to reduce ubiquitination and increase their protein stability. Furthermore, the severity of NAFLD induced by an HFD and NASH induced by a fructose/palmitate/cholesterol/trans-fat (FPC) diet was significantly ameliorated in hepatocyte-specific USP15 knockout mice. Thus, our findings reveal an unrecognized function of USP15 in the lipid accumulation of livers, which exacerbates NAFLD to NASH by overriding nutrients and inducing inflammation. Therefore, targeting USP15 can be used in the prevention and treatment of NAFLD and NASH.

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Section: Introductionmentioning

confidence: 99%

Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

et al. 2023

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“…Previously, we comprehensively analyzed the vital role of USP1 in HCC and identified it as a promising therapeutic target with good prognostic value [ 34 ]. After that, researchers focused more attention on the novel functions of USP1 in HCC and other liver diseases [ [35] , [36] , [37] , [38] , [39] ]. Recently, Du et al.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of hepatocytes reveals the association between ubiquitin-specific peptidase 1 and yes-associated protein 1 during liver regeneration

Zhao

Zhang

et al. 2023

Regenerative Therapy

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“…However, most patients will develop resistance to lenvatinib ( 77 ), so research on the mechanism of drug resistance in patients will help the development of targeted therapy for liver cancer ( 78 ). USP1 can promote the proliferation and migration of HCC cells by promoting the expression and stability of c-kit protein, and USP1 also promotes the efficacy of lenvatinib in HCC ( 79 ). In conclusion, USP1, as a novel diagnostic and predictive marker in the treatment of liver cancer, can provide new ideas for the development of targeted drugs for liver cancer treatment.…”

Section: Ubiquitin-specific Proteasementioning

confidence: 99%

Research Progress of DUB Enzyme in Hepatocellular Carcinoma

et al. 2022

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According to GLOBOCAN 2021 cancer incidence and mortality statistics compiled by the International Agency for Research on Cancer, hepatocellular carcinoma (HCC) is the most common malignancy in the human liver and one of the leading causes of cancer death worldwide. Although there have been great advances in the treatment of HCC, such as regofenib, sorafenib, and lomvatinib, which have been developed and approved for the clinical treatment of advanced or metastatic HCC. However, they only prolong survival by a few months, and patients with advanced liver cancer are susceptible to tumor invasion metastasis and drug resistance. Ubiquitination modification is a type of post-translational modification of proteins. It can affect the physiological activity of cells by regulating the localization, stability and activity of proteins, such as: gene transcription, DNA damage signaling and other pathways. The reversible process of ubiquitination is called de-ubiquitination: it is the process of re-releasing ubiquitinated substrates with the participation of de-ubiquitinases (DUBs) and other active substances. There is growing evidence that many dysregulations of DUBs are associated with tumorigenesis. Although dysregulation of deuquitinase function is often found in HCC and other cancers, The mechanisms of action of many DUBs in HCC have not been elucidated. In this review, we focused on several deubiquitinases (DUBs) associated with hepatocellular carcinoma, including their structure, function, and relationship to hepatocellular carcinoma. hepatocellular carcinoma was highlighted, as well as the latest research reports. Among them, we focus on the USP family and OTU family which are more studied in the HCC. In addition, we discussed the prospects and significance of targeting DUBs as a new strategy for the treatment of hepatocellular carcinoma. It also briefly summarizes the research progress of some DUB-related small molecule inhibitors and their clinical application significance as a treatment for HCC in the future.

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Ubiquitin-specific protease 1 acts as an oncogene and promotes lenvatinib efficacy in hepatocellular carcinoma by stabilizing c-kit

Cited by 11 publications

References 25 publications

Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Transcriptomic analysis of hepatocytes reveals the association between ubiquitin-specific peptidase 1 and yes-associated protein 1 during liver regeneration

Research Progress of DUB Enzyme in Hepatocellular Carcinoma

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