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Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Oct 27, 2025; 17(10): 111454
Published online Oct 27, 2025. doi: 10.4240/wjgs.v17.i10.111454
Reduction in the hepatocellular carcinoma antioncogene SLC39A14 during the malignant progression of hepatocellular carcinoma
Wei Guo, Ming-Xuan Wang, Tong Mu, Kan Xu, Zhao-Di Jiang, Xue-Hua Wan, Jun-Wei Li, Yong-Xiang Yi
Wei Guo, Ming-Xuan Wang, Tong Mu, Kan Xu, Zhao-Di Jiang, Xue-Hua Wan, Department of Infectious Disease and Liver Disease, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
Jun-Wei Li, Yong-Xiang Yi, Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing 211113, Jiangsu Province, China
Yong-Xiang Yi, Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
Co-corresponding authors: Jun-Wei Li and Yong-Xiang Yi.
Author contributions: Guo W performed the experiments and wrote the manuscript; Wang MX, Jiang ZD and Mu T collected the clinical samples and clinical information; Xu K and Wan XH performed the in vivo experiments; Yi YX and Li JW designed the study and revised the manuscript. All the authors contributed to the article and approved the manuscript for submission. Prof. Yi YX, as the clinical research lead, assumed primary responsibility for the comprehensive design of clinical trials, including protocol development, ethical approval acquisition, patient screening and recruitment strategies, clinical data collection and validation processes, as well as the interpretation of patient-derived findings. On the experimental research front, Prof. Li JW directed all laboratory-based investigations, overseeing experimental design formulation, methodology optimization, molecular mechanism exploration, data analysis pipelines, and the validation of key mechanistic hypotheses through rigorous bench science approaches. Beyond their specialized supervisory roles in these respective areas, both corresponding authors collaboratively ensured the maintenance of the highest academic standards throughout the manuscript development process. This joint oversight included critical evaluation of the theoretical framework, methodological rigor, data interpretation accuracy, and the overall scientific narrative. Additionally, they played pivotal roles in securing the necessary financial support for this multifaceted research program through competitive grant applications and institutional funding allocations. Their combined intellectual input, resource provision, and continuous mentorship were absolutely fundamental to the successful execution and timely completion of this comprehensive research endeavor, which bridges important gaps between clinical observations and fundamental biological mechanisms.
Supported by Postgraduate Research & Practice Innovation Program of Jiangsu Province, No. SJCX23-0857.
Institutional review board statement: The study was reviewed and approved by the Research Ethics Committee of The Second Hospital of Nanjing Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Care and Utilization Committee of Nanjing University of Chinese Medicine [IACUC protocol number: (Protocol No. 2024AE01044)].
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: No additional data are available.
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: Yong-Xiang Yi, MD, PhD, Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, No. 1 Kangfu Road, Tangshan Subdistrict, Jiangning District, Nanjing 211113, Jiangsu Province, China. ian0126@126.com
Received: July 1, 2025
Revised: August 1, 2025
Accepted: August 25, 2025
Published online: October 27, 2025
Processing time: 116 Days and 18.1 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality owing to its mechanistic complexity and individual heterogeneity, making early diagnosis challenging. The role of SLC39A14, a biomarker for multiple tumors, in HCC remains to be elucidated.

AIM

To determine the tumor-suppressive role of SLC39A14 in HCC and its underlying molecular mechanisms.

METHODS

The expression pattern of SLC39A14 in HCC was evaluated using quantitative reverse transcriptase PCR and western blotting, and its association with tumor malignancy was further validated in C57BL/6J mouse HCC model. A series of functional assays, including cell counting kit-8, colony formation, apoptosis, scratch, and invasion tests, were conducted to assess how alterations in the SLC39A14 expression affect the oncological behavior of HCC cells. In addition, bioinformatics analysis was performed to investigate the potential regulatory mechanism underlying SLC39A14 expression in HCC.

RESULTS

The protein expression and RNA abundance of SLC39A14 in human HCC tissues were significantly lower than those in paracancerous tissues (P < 0.01). In HCC model mice, the SLC39A14 expression decreased gradually as the disease progressed. The overexpression of SLC39A14 significantly inhibited the proliferation, migration, and invasion of Huh7 HCC cells while promoting their apoptosis. The knockdown of SLC39A14 exerted the opposite effect. Bioinformatics analysis suggested the involvement of the transcription factor STAT3 in regulating the SLC39A14 expression.

CONCLUSION

SLC39A14 dysregulation promotes HCC progression through BCL-2/BAX/Caspase-3 apoptotic axis and epithelial–mesenchymal transition transformation axis, suggesting potential therapeutic targets.

Keywords: SLC39A14; Apoptosis; Epithelial–mesenchymal transition; Hepatocellular carcinoma

Core Tip: This study's findings associate SLC39A14 downregulation with hepatocellular carcinoma (HCC) progression. SLC39A14 overexpression inhibits HCC cell proliferation, migration, and invasion while promoting apoptosis via the BCL-2/BAX/caspase-3 pathway. Bioinformatics analysis suggests that STAT3 regulates the expression of SLC39A14. Our findings together highlight SLC39A14-BCL-2/BAX/caspase-3 and SLC39A14-EMT axes as potential therapeutic targets for HCC.