UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway

Huhu Zhang; Jiahua Yang; Qinghang Song; Xiaoyan Ding; Fulin Sun; Lina Yang

doi:10.3724/abbs.2024014

UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway

Acta Biochim Biophys Sin (Shanghai). 2024 Feb 25;56(2):199-209. doi: 10.3724/abbs.2024014.

Authors

Huhu Zhang¹, Jiahua Yang^{2

3}, Qinghang Song⁴, Xiaoyan Ding¹, Fulin Sun⁴, Lina Yang¹

Affiliations

¹ Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao 266071, China.
² School of Basic Medicine, Qingdao University, Qingdao 266071, China.
³ Institute of Brain Science and Disease, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao 266071, China.
⁴ College of Medicine, Qingdao University, Qingdao 266071, China.

Abstract

Intrahepatic cholangiocarcinoma (ICC) accounts for approximately 15% of primary liver cancers, and the incidence rate has been increasing in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to identify signature genes. The aim of this study is to screen the signature genes of ICC and find the potential target for the treatment of ICC. We find that UBA3 is highly expressed in ICC, and knockdown of UBA3 inhibits ICC proliferation, invasion and migration. Mechanistic experiments show that UBA3 promotes ICC proliferation, invasion and migration by affecting ANXA2 through the MAPK signaling pathway. UBA3 is a target of bufalin, and bufalin targeting UBA3 inhibits ICC development and progression through the MAPK signaling pathway. In conclusion, our study shows that bufalin inhibits ICC by targeting UBA3, which has emerged as a new biomarker and potential therapeutic target for ICC.

Keywords: ANXA2; UBA3; bufalin; intrahepatic cholangiocarcinoma; migration; prognosis; proliferation.

MeSH terms

Bile Duct Neoplasms* / genetics
Bile Duct Neoplasms* / pathology
Bile Ducts, Intrahepatic / pathology
Cell Line, Tumor
Cell Proliferation
Cholangiocarcinoma* / genetics
Cholangiocarcinoma* / pathology
Humans
Signal Transduction
Ubiquitin-Activating Enzymes* / genetics
Ubiquitin-Activating Enzymes* / metabolism

Substances

NAE protein, human
Ubiquitin-Activating Enzymes

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (No. 81803895), Shandong Province Natural Science Foundation (No. ZR2021YQ57) and China Postdoctoral Science Foundation (Nos. 2020M682131 and 2021T140357).