Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Mar 24, 2025; 16(3): 94091
Published online Mar 24, 2025. doi: 10.5306/wjco.v16.i3.94091
Transmembrane channel-like 5 drives hepatocellular carcinoma progression by regulating epithelial-mesenchymal transition
Jiao Li, Zi-Yu Wang, Yan Jin, Jing Xu, Yun-Jin Ya, Ting-Qiu Wan, Xi Li, Xi Wang
Jiao Li, Zi-Yu Wang, Yan Jin, Jing Xu, Yun-Jin Ya, Ting-Qiu Wan, Xi Li, Xi Wang, Department of Hepatobiliary Surgery, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650500, Yunnan Province, China
Co-first authors: Jiao Li and Zi-Yu Wang.
Co-corresponding authors: Yan Jin and Jing Xu.
Author contributions: Li J and Wang ZY contribute equally to this study as co-first authors; Jin Y and Xu J contribute equally to this study as co-corresponding authors; Li J, Wang ZY, Xu J, and Jin Y conceived and designed the experiments; Li J, Wang ZY, Ya YJ, Wan TQ, Li X, and Wang X performed the experiments; Li J and Wang ZY analyzed the data; Xu J and Jin Y contributed to data curation; Li J and Wang ZY contributed to original draft; Ya YJ, Wan TQ, Li X, Wang X, Xu J, and Jin Y contributed to review and edit.
Supported by the Yunnan Provincial Department of Science and Technology-Kunming Medical University Joint Special Project on Applied Basic Research, No. 202401AY070001-132; the Yunnan Provincial Science Foundation, No. 2018FE001(-287), National Natural Science Foundation of China, No. 81460443; and the Ten Thousand People Plan of Yunnan Province, No. KH-SWR-MY-2020-002.
Institutional review board statement: The study was approved by the Affiliated Hospital of Kunming University of Science and Technology.
Institutional animal care and use committee statement: The study was approved by the Ethics Committee of the Affiliated Hospital of Kunming University of Science and Technology.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Data sharing statement: The datasets analyzed during the current study are available from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Yan Jin, Chief Physician, Department of Hepatobiliary Surgery, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming 650500, Yunnan Province, China. 13312503258@163.com
Received: March 11, 2024
Revised: October 17, 2024
Accepted: November 25, 2024
Published online: March 24, 2025
Processing time: 315 Days and 23.4 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is a difficult cancer to manage due to its highly invasive and metastatic nature.

AIM

To investigate the molecular function of transmembrane channel-like 5 (TMC5) in vitro and in vivo, with the objective of identifying novel diagnosis and treatment targets for HCC.

METHODS

The expression of TMC in cancer and normal tissues, along with its correlation with HCC prognosis, was analyzed using the GENT2, GEPIA database, and Human Protein Atlas. COX analysis was conducted to assess the relationship between TMC5 expression and overall survival in TCGA-LIHC patients. Further experiments were conducted to investigate the effect of TMC5 in cancer progression through loss- and gain-of-function assays in vitro and in vivo.

RESULTS

Bioinformatics revealed that TMC5 expression was generally higher in tumors than in normal tissues, and its expression was associated with poorer patient survival outcomes. TMC5 expression in HCC tissues and cells was consistent with the results of the bioinformatics analysis. Suppression of TMC5 expression reduced migration, invasion, and proliferation, while also decreasing the expression of epithelial-mesenchymal transition (EMT)-associated molecules in MHCC97-LM3 cells. Conversely, higher TMC5 expression significantly increased cell migration, invasion, proliferation, and EMT in MHCC97 L cells. TMC5 knockdown significantly decreased both the formation and spread of nodules in liver tissue, whereas TMC5 overexpression promoted them.

CONCLUSION

Our study provides compelling evidence that TMC5 is highly expressed in HCC and drives cancer progression through the activation of EMT-mediated invasion. TMC5 could represent a valuable molecular target for the diagnosis and treatment of HCC.

Keywords: Hepatocellular carcinoma; Transmembrane channel-like protein 5; Epithelial-mesenchymal transition; Bioinformatics; diagnosis; Prognosis

Core Tip: In this study, transmembrane channel-like 5 (TMC5), which is highly expressed in hepatocellular carcinoma (HCC) and associated with increased invasive migration ability, is proposed for the first time as a potential marker for HCC. Bioinformatics analysis and in vivo and in vitro experiments confirmed that TMC5 regulates epithelial-mesenchymal transition to promote invasive migration in HCC. TMC5 might be a valuable molecular target for HCC diagnosis and treatment.