TC2N Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Targeting the Wnt/I3-Catenin Signaling Pathway

作者全名："Lou, Yi-Xia; Gu, Jing; Zhu, Lei; Sun, Sheng-Qi; Hao, Xiang-Lin; Chen, Jian-Ping; Han, Fei; Wang, Dan-Dan; Jiang, Xiao; Liu, Jin-Yi"

作者地址："[Lou, Yi-Xia; Gu, Jing; Zhu, Lei; Sun, Sheng-Qi; Chen, Jian-Ping; Wang, Dan-Dan; Jiang, Xiao; Liu, Jin-Yi] Third Mil Med Univ, Army Med Univ, Coll Prevent Med, Inst Toxicol, Chongqing, Peoples R China; [Hao, Xiang-Lin] Third Mil Med Univ, Army Med Univ, Xinqiao Hosp, Dept Pathol, Chongqing 400037, Peoples R China; [Han, Fei] Chongqing Med Univ, Sch Publ Hlth, Dept Toxicol, Chongqing, Peoples R China; [Wang, Dan-Dan] Henan Univ, Henan Prov Engn Ctr Tumor Mol Med, Sch Basic Med, Lab Cell Signal Transduct, Kaifeng, Peoples R China"

通信作者："Liu, JY (通讯作者)，Third Mil Med Univ, Army Med Univ, Coll Prevent Med, Inst Toxicol, Chongqing, Peoples R China."

来源：LABORATORY INVESTIGATION

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001108318600001

JCR分区：Q1

影响因子：5.1

年份：2023

卷号：103

期号：12

开始页：　

结束页：　

文献类型：Article

关键词：hepatocellular carcinoma; metastasis; proliferation; TC2N; Wnt/I3-catenin pathway

摘要："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/I3-catenin signaling pathway. Mechanistically, TC2N activated the Wnt/I3-catenin signaling pathway by regulating the expression levels of I3-catenin and its downstream targets CyclinD1, MMP7, c-Myc, c-Jun, AXIN2, and glutamine synthase. Furthermore, the deletion of I3-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/I3-catenin signaling pathway, indicating that TC2N might be a potential molecular target for the treatment of HCC.(c) 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved."

基金机构："National Natural Science Foundation of China [82002446, 81902711]"

基金资助正文：<BOLD>Funding</BOLD> This work was supported by the National Natural Science Foundation of China (No. 82002446 and 81902711) .