2. Academic Validation
  3. NUP37 accumulation mediated by TRIM28 enhances lipid synthesis to accelerate HCC progression

NUP37 accumulation mediated by TRIM28 enhances lipid synthesis to accelerate HCC progression

  • Oncogene. 2024 Oct;43(44):3255-3267. doi: 10.1038/s41388-024-03167-1.
Zhiyi Liu # 1 2 3,  Qinghe Hu # 1 2 3,  Qing Luo 1 2 3,  Guowei Zhang 1 2 3,  Weichao Yang 1 2 3,  Kuan Cao 1 2 3,  Ruqiao Fang 1 2 3,  Renhao Wang 4 5 6,  Hengliang Shi 7 8 9 10,  Bin Zhang 11 12 13
Affiliations

Affiliations

  • 1 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 2 Research Center of Digestive Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 3 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 4 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China. wangrenhao@xzhmu.edu.cn.
  • 5 Research Center of Digestive Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. wangrenhao@xzhmu.edu.cn.
  • 6 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. wangrenhao@xzhmu.edu.cn.
  • 7 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China. shl@xzhmu.edu.cn.
  • 8 Research Center of Digestive Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. shl@xzhmu.edu.cn.
  • 9 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. shl@xzhmu.edu.cn.
  • 10 Central Laboratory, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. shl@xzhmu.edu.cn.
  • 11 Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China. zhangbin@xzhmu.edu.cn.
  • 12 Research Center of Digestive Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. zhangbin@xzhmu.edu.cn.
  • 13 Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. zhangbin@xzhmu.edu.cn.
  • # Contributed equally.
PMID: 39294431 DOI: 10.1038/s41388-024-03167-1
Abstract

Elevated intracellular lipid synthesis is important for hepatocellular carcinoma (HCC) progression. Our study aimed to identify the role of nucleoporin 37 (NUP37) in lipid synthesis and HCC progression. The expression of NUP37 was significantly upregulated in HCC and associated with a poor prognosis. NUP37 silencing suppressed lipid synthesis, proliferation, migration, and invasion of HCC cells in vitro, and restrained tumor growth in xenograft mouse models in vivo. Next, we found the high expression of NUP37 in HCC was related to post-translational modifications. Tripartite motif-containing 28 (TRIM28) was identified as an interacting protein of NUP37 and upregulated its protein level. The subsequent analysis revealed that TRIM28-mediated SUMOylation of NUP37 at Lys114/118/246 inhibited K27-linked polyubiquitination of NUP37, which is one reason for its high expression level in HCC. In conclusion, TRIM28 SUMOylates NUP37 to prevent its ubiquitination and proteasomal degradation, increasing the stability of the NUP37 protein, thereby promoting lipid synthesis and the progression of HCC.

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