Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Research Center of Digestive Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Oncogene. 2024 Oct;43(44):3255-3267. doi: 10.1038/s41388-024-03167-1. Epub 2024 Sep 18.
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.
细胞内脂质合成升高对肝细胞癌（HCC）的进展很重要。我们的研究旨在确定核孔蛋白 37（NUP37）在脂质合成和 HCC 进展中的作用。NUP37 的表达在 HCC 中显著上调，并与预后不良相关。NUP37 沉默抑制 HCC 细胞在体外的脂质合成、增殖、迁移和侵袭，并在体内异种移植小鼠模型中抑制肿瘤生长。接下来，我们发现 HCC 中 NUP37 的高表达与翻译后修饰有关。三结构域含 28 （TRIM28）被鉴定为 NUP37 的相互作用蛋白，并上调其蛋白水平。随后的分析表明，TRIM28 介导的 NUP37 在 Lys114/118/246 处的 SUMO 化抑制了 NUP37 的 K27 连接多泛素化，这是其在 HCC 中高表达的原因之一。总之，TRIM28 对 NUP37 进行 SUMO 化，以防止其泛素化和蛋白酶体降解，从而增加 NUP37 蛋白的稳定性，从而促进脂质合成和 HCC 的进展。
