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nature portfolio privacy policy guowang xu & hai-long piao high-fat diet-driven hcc advertising halting solutions mhcc-97h-related stable cells transforming pgex-4t-1-gst-pparγ usp22–pparγ/acc/acly axis contributed usp8-mediated ubiquitination-dependent degradation mhcc-97l-related stable cells research ethics committee nature 373 nature usp22-overexpressing mhcc-97l cells usp22-transduced mhcc-97l cells usp22-knockdown mhcc-97h cells mhcc-97l-usp22 c185s cells reprints integrating single-cell rna-seq biomedical research research design flag-pparγ-5kr transduced cells quantitative real-time pcr mhcc-97h cells transduced usp22-overexpressing mhcc-97l sera-mag magnetic olido small-molecule inhibitors targeting mhcc-97l cells transduced dual-luciferase reporter assay lc-ms/ms data mhcc-97h-shusp22-1/2 cells mhcc-97h-shusp22 cells flag-pparγ-5kr overexpression cells de novo synthesis mass spectrometry conditions twenty ms/ms scans usp22-pparγ-acly/acc axis research mhcc-97l cell lines resulting ms/ms data shcontrol mhcc-97h cells nontargeted metabolomic analysis usp22-engineereed stable cells ch/index integrative pan-cancer analysis bulk rna-seq data cancer-related deaths worldwide hai-long piao finally palmitic acid

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         headline:USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma
         description:Elevated de novo lipogenesis is considered to be a crucial factor in hepatocellular carcinoma (HCC) development. Herein, we identify ubiquitin-specific protease 22 (USP22) as a key regulator for de novo fatty acid synthesis, which directly interacts with deubiquitinates and stabilizes peroxisome proliferator-activated receptor gamma (PPARγ) through K48-linked deubiquitination, and in turn, this stabilization increases acetyl-CoA carboxylase (ACC) and ATP citrate lyase (ACLY) expressions. In addition, we find that USP22 promotes de novo fatty acid synthesis and contributes to HCC tumorigenesis, however, this tumorigenicity is suppressed by inhibiting the expression of PPARγ, ACLY, or ACC in in vivo tumorigenesis experiments. In HCC, high expression of USP22 positively correlates with PPARγ, ACLY or ACC expression, and associates with a poor prognosis. Taken together, we identify a USP22-regulated lipogenesis mechanism that involves the PPARγ-ACLY/ACC axis in HCC tumorigenesis and provide a rationale for therapeutic targeting of lipogenesis via USP22 inhibition. Different deubiquitinases are associated to cancer development. Here, the authors show that PPARgamma is stabilized by USP22-mediated deubiquitination leading to lipid accumulation and promoting hepatocellular carcinoma.
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      headline:USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma
      description:Elevated de novo lipogenesis is considered to be a crucial factor in hepatocellular carcinoma (HCC) development. Herein, we identify ubiquitin-specific protease 22 (USP22) as a key regulator for de novo fatty acid synthesis, which directly interacts with deubiquitinates and stabilizes peroxisome proliferator-activated receptor gamma (PPARγ) through K48-linked deubiquitination, and in turn, this stabilization increases acetyl-CoA carboxylase (ACC) and ATP citrate lyase (ACLY) expressions. In addition, we find that USP22 promotes de novo fatty acid synthesis and contributes to HCC tumorigenesis, however, this tumorigenicity is suppressed by inhibiting the expression of PPARγ, ACLY, or ACC in in vivo tumorigenesis experiments. In HCC, high expression of USP22 positively correlates with PPARγ, ACLY or ACC expression, and associates with a poor prognosis. Taken together, we identify a USP22-regulated lipogenesis mechanism that involves the PPARγ-ACLY/ACC axis in HCC tumorigenesis and provide a rationale for therapeutic targeting of lipogenesis via USP22 inhibition. Different deubiquitinases are associated to cancer development. Here, the authors show that PPARgamma is stabilized by USP22-mediated deubiquitination leading to lipid accumulation and promoting hepatocellular carcinoma.
      datePublished:2022-04-21T00:00:00Z
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         Cancer metabolism
         Science
         Humanities and Social Sciences
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      email:[email protected]
      name:Hai-long Piao
      url:http://orcid.org/0000-0001-7451-0386
      affiliation:
            name:Dalian Institute of Chemical Physics, Chinese Academy of Sciences
            address:
               name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
               type:PostalAddress
            type:Organization
            name:University of Chinese Academy of Sciences
            address:
               name:University of Chinese Academy of Sciences, Beijing, China
               type:PostalAddress
            type:Organization
            name:China Medical University
            address:
               name:Department of Biochemistry & Molecular Biology, School of Life Sciences, China Medical University, Shenyang, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, China
      name:The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China
      name:Liaoning Key Laboratory of Molecular Targeted Drugs in Hepatobiliary and Pancreatic Cancer, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
      name:University of Chinese Academy of Sciences, Beijing, China
      name:Department of Biochemistry & Molecular Biology, School of Life Sciences, China Medical University, Shenyang, China

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