2. Academic Validation
  3. USP49 regulates lipid metabolism in hepatocellular carcinoma by stabilizing RACK1 to promote tumor proliferation and migration

USP49 regulates lipid metabolism in hepatocellular carcinoma by stabilizing RACK1 to promote tumor proliferation and migration

  • Biochim Biophys Acta Mol Cell Res. 2026 Mar;1873(3):120107. doi: 10.1016/j.bbamcr.2026.120107.
Weikang Xu 1,  Jijun Shan 2,  Jifei Wang 3,  Yudi Zhou 4,  Yiming Ouyang 1,  Yananlan Chen 5,  Qiyang Zhou 6
Affiliations

Affiliations

  • 1 Department of General Surgery, Suzhou Ninth People's Hospital, Soochow University, Suzhou, Jiangsu, China.
  • 2 Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 3 Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 4 Department of General Surgery, The Fourth Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
  • 5 Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
  • 6 Department of General Surgery, Suzhou Ninth People's Hospital, Soochow University, Suzhou, Jiangsu, China. Electronic address: [email protected].
PMID: 41519241 DOI: 10.1016/j.bbamcr.2026.120107
Abstract

Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited therapeutic options. While ubiquitin-specific peptidase 49 (USP49) has been implicated in various cancers, its role in HCC is unclear. Here, we found that USP49 is upregulated in HCC tissues and associated with poor prognosis. Functional assays demonstrated that USP49 promotes HCC proliferation and migration both in vitro and in vivo. Mechanistically, USP49 directly interacts with and deubiquitinates RACK1, thereby stabilizing it. This stabilization leads to RACK1-driven transcriptional activation of key fatty acid metabolic Enzymes, enhancing triglyceride synthesis and fueling tumor growth through metabolic reprogramming. Collectively, our study identifies the USP49/RACK1 axis as a critical driver of HCC progression and nominates USP49 as a promising therapeutic target.

Keywords

Deubiquitylation; Hepatocellular carcinoma; Lipid metabolism; USP49.

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