Tian HP, Wu TH, Zhang GJ, Li SJ. Transcription factor 3 enhances hepatocellular carcinoma metastasis by upregulating matrix metalloproteinase-11. World J Gastrointest Oncol 2025; 17(9): 110527 [DOI: 10.4251/wjgo.v17.i9.110527]
Corresponding Author of This Article
Sheng-Jie Li, Professor, Department of Colorectal Surgery, University of Health and Rehabilitation Sciences, Qingdao Municipal Hospital, No. 5 Donghai Zhong Road, Qingdao 266000, Shandong Province, China. lishengjieq@163.com
Research Domain of This Article
Cell Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Hong-Peng Tian, Tian-Hao Wu, Guang-Jun Zhang, Sheng-Jie Li
Hong-Peng Tian, Tian-Hao Wu, Guang-Jun Zhang, Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Hong-Peng Tian, Tian-Hao Wu, Guang-Jun Zhang, Sheng-Jie Li, National Clinical Key Specialty (General Surgery), Sub-center of National Clinical Research Center for Digestive Diseases Sichuan Clinical Research Center for Digestive Diseases, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Sheng-Jie Li, Department of Colorectal Surgery, University of Health and Rehabilitation Sciences, Qingdao Municipal Hospital, Qingdao 266000, Shandong Province, China
Co-first authors: Hong-Peng Tian and Tian-Hao Wu.
Co-corresponding authors: Guang-Jun Zhang and Sheng-Jie Li.
Author contributions: Tian HP wrote the paper; Tian HP and Wu TH performed the experiments and data analysis as the co-first authors of the paper; Zhang GJ and Li SJ conceived and designed the study as the co-corresponding authors; Li SJ reviewed and edited the manuscript; all authors read and approved the final manuscript.
Supported by Sichuan Clinical Key Specialty, No. 2017JQ0039 and No. 2017KZ0028.
Institutional review board statement: The present study was approved by the Medical Ethical Committee of the Affiliated Hospital of North Sichuan Medical College, No. 2016ER(A)008.
Institutional animal care and use committee statement: The animal experiments were approved by the Animal Ethical Committee of the Affiliated Hospital of North Sichuan Medical College.
Conflict-of-interest statement: The authors declared that they had no conflicts of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Dataset available from the corresponding author at lishengjieq@163.com.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sheng-Jie Li, Professor, Department of Colorectal Surgery, University of Health and Rehabilitation Sciences, Qingdao Municipal Hospital, No. 5 Donghai Zhong Road, Qingdao 266000, Shandong Province, China. lishengjieq@163.com
Received: June 10, 2025 Revised: July 6, 2025 Accepted: August 6, 2025 Published online: September 15, 2025 Processing time: 99 Days and 3.1 Hours
Abstract
BACKGROUND
Transcription factor 3 (TCF3) has a vital role in tumor occurrence and progression. However, the specific functions and underlying mechanisms of dysregulated TCF3 in hepatocellular carcinoma (HCC) have not been not thoroughly characterized. Thus, we explored the roles of TCF3 in HCC.
AIM
To explore the roles of TCF3 in HCC.
METHODS
TCF3 knockdown and overexpression models were developed via lentiviral vectors in HCC cells. Transwell and in vivo metastasis experiments were performed to measure the effects of TCF3 on HCC cell metastasis. Then, reverse transcription-quantitative polymerase chain reaction, serial deletion, western blotting, site-directed mutagenesis, chromatin immunoprecipitation, and dual-luciferase reporter assays were done to determine the pathomechanisms.
RESULTS
TCF3 levels were markedly elevated in HCC samples and correlated with poor prognosis. Furthermore, overexpression of TCF3 promoted HCC cell invasion as well as migration, while TCF3 knockdown repressed HCC cell growth. In addition, TCF3 interacted with the promoter region of matrix metalloproteinase-11 (MMP11), facilitating the transcriptional activation of MMP11 mRNA, which consequently enhanced the expression of MMP11. MMP11 knockdown repressed TCF3-associated HCC cell migration and invasion, while its overexpression attenuated the TCF3 knockdown-mediated repression of HCC growth. In human-derived HCC samples, TCF3 was positively correlated with MMP11 expression levels.
CONCLUSION
TCF3 was significantly upregulated in HCC. TCF3 overexpression enhanced HCC cell invasion and metastasis through transactivation of MMP11 expression. TCF3 could be a prognostic biomarker and regulator of HCC metastasis.
Core Tip: Elevated transcription factor 3 (TCF3) levels were observed in hepatocellular carcinoma (HCC) samples and were associated with unfavorable outcomes. Additionally, overexpression of TCF3 facilitated the invasion and migration of HCC cells, while knocking down TCF3 suppressed their growth. In addition, TCF3 interacts with the promoter region of matrix metalloproteinase-11 (MMP11), facilitating the transcriptional activation of MMP11 mRNA, which consequently enhances the expression of MMP11. MMP11 knockdown repressed TCF3-associated HCC cell migration and invasion, while its overexpression attenuated the TCF3 knockdown-mediated repression of HCC growth. In human-derived HCC samples, TCF3 was positively correlated with MMP11 expression levels.
