NXN suppresses metastasis of hepatocellular carcinoma by promoting degradation of Snail through binding to DUB3
-
Published:2022-08-04
Issue:8
Volume:13
Page:
-
ISSN:2041-4889
-
Container-title:Cell Death & Disease
-
language:en
-
Short-container-title:Cell Death Dis
Author:
Zhang Yuanping, Zuo Dinglan, Qiu Jiliang, Li Kai, Niu Yi, Yuan Yichuan, Qiu Yuxiong, Qiao Liang, He Wei, Wang Chenwei, Yuan YunfeiORCID, Li BinkuiORCID
Abstract
AbstractThe poor prognosis of hepatocellular carcinoma (HCC) could be attributed to its high metastasis rate. Here, we report the role of nucleoredoxin (NXN), a multifunctional redox-active protein, in HCC metastasis. The expression of NXN in HCC tissues was measured by immunohistochemistry. The role of NXN on HCC proliferation was determined by CCK-8, EdU and colony formation assays in vitro and subcutaneous tumor formation model in vivo. Transwell and wound healing assays and tail vein injection model were performed to assess the function of NXN on HCC metastasis. Co-immunoprecipitation assay was performed to examine the interaction among NXN, Snail and DUB3. Our results showed that NXN was downregulated in HCC tissues compared to adjacent liver tissues. Patients with low NXN expression had shorter overall survival (OS) time (P < 0.001) than those with high NXN expression. Biologically, ectopic expression of NXN significantly inhibited the proliferation and metastasis of HCC cells both in vitro and in vivo by suppressing epithelial-mesenchymal transition (EMT). Mechanistically, NXN promoted the ubiquitin-proteasome-mediated degradation of Snail through interaction with DUB3. Further, depletion of Snail abolished NXN-inhibited cell proliferation and metastasis. In summary, NXN suppressed the proliferation and metastasis of HCC by inhibiting DUB3-mediated deubiquitylation of Snail protein. Our study demonstrates that NXN, DUB3 and Snail complex functioned as an important regulatory mechanism of HCC progression and indicates a potential therapeutic approach for the treatment of HCC metastasis.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Reference35 articles.
1. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32. 2. Li N, Wu P, Shen Y, Yang C, Zhang L, Chen Y, et al. Predictions of mortality related to four major cancers in China, 2020 to 2030. Cancer Commun. 2021;41:404–13. 3. Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, et al. Hepatocellular carcinoma. Nat Rev Dis Prim. 2016;2:1–23. 4. Xu XF, Xing H, Han J, Li ZL, Lau WY, Zhou YH, et al. Risk Factors, Patterns, and Outcomes of Late Recurrence After Liver Resection for Hepatocellular Carcinoma: A Multicenter Study From China. JAMA Surg. 2019;154:209–17. 5. Nieto MA, Huang Ruby Y-J, Jackson Rebecca A, Thiery Jean P. Emt: 2016. Cell. 2016;166:21–45.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|