TC2N Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Targeting the Wnt/β-Catenin Signaling Pathway.

Autor: Lou YX; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China., Gu J; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China., Zhu L; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China., Sun SQ; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China., Hao XL; Department of Pathology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China., Chen JP; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China., Han F; Department of Toxicology, School of Public Health, Chongqing Medical University, Chongqing, China., Wang DD; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China; Laboratory of Cell Signal Transduction, Henan Provincial Engineering Centre for Tumor Molecular Medicine, School of Basic Medicine, Henan University, Kaifeng, China., Jiang X; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China., Liu JY; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address: jinyiliutmmu@163.com.
Jazyk: angličtina
Zdroj: Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2023 Dec; Vol. 103 (12), pp. 100260. Date of Electronic Publication: 2023 Oct 13.
DOI: 10.1016/j.labinv.2023.100260
Abstrakt: Hepatocellular carcinoma (HCC), one of the most prevalent types of cancer worldwide, has an exceedingly poor prognosis. Tandem C2 domain nuclear protein (TC2N) has been implicated in tumorigenesis and serves as an oncogene or tumor suppressor in different types of cancer. Here, we explore the possible regulatory activities and molecular mechanisms of TC2N in HCC progression. However, TC2N expression was significantly upregulated in HCC tissues and hepatoma cell lines, and this upregulation was positively correlated with tumor progression in HCC patients. The ectopic overexpression of TC2N accelerated the proliferation, migration, and invasion of HCC cells, whereas its knockdown showed the opposite effects. Bioinformatics analysis showed that TC2N participates in the regulation of the Wnt/β-catenin signaling pathway. Mechanistically, TC2N activated the Wnt/β-catenin signaling pathway by regulating the expression levels of β-catenin and its downstream targets CyclinD1, MMP7, c-Myc, c-Jun, AXIN2, and glutamine synthase. Furthermore, the deletion of β-catenin effectively neutralized the regulation of TC2N in HCC proliferation and metastasis. Overall, this study showed that TC2N promotes HCC proliferation and metastasis by activating the Wnt/β-catenin signaling pathway, indicating that TC2N might be a potential molecular target for the treatment of HCC.
(Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE