Abstract
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a poor prognosis, underscoring the urgent need to identify novel therapeutic targets. The epigenetic regulator TET1, a key enzyme involved in active DNA demethylation, has been implicated in various cancers, however, its precise role in HCC remains controversial and poorly defined. This study demonstrates that TET1 is significantly upregulated in HCC tissues, and elevated TET1 expression is associated with advanced tumor stage, shorter overall survival and reduced disease-free survival in patients. Functional assays revealed that TET1 knockdown significantly suppressed HCC cell proliferation and induced apoptosis; it also triggered G1-phase cell cycle arrest. Mechanistically, we found that the oncogenic effects of TET1 are mediated through activation of the PI3K/Akt signaling pathway. In summary, our results establish TET1 as a critical promoter of HCC progression and elucidate its role in regulating the PI3K/Akt pathway. These findings highlight its value as both a prognostic biomarker and a potential therapeutic target in HCC.
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Data availability
All relevant data supporting the findings of this study are included within the manuscript and its Supplementary material File. Other raw data generated during this study that are reasonably requested are available from the corresponding author upon request.
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Funding
This work was supported by the Key Program of Health Commission of Anhui Province under Grant No. AHWJ2022a034 and the Project of Suzhou Municipal Health Commission under Grant No. SZWJ2024a052.
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The authors’ contributions are as follows: S.Q. (lead): Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Writing – original draft, Visualization. M.C. (supporting): Resources, Supervision, Writing – review & editing. Z.D. (supporting): Investigation, Validation. M.D. (supporting): Software, Formal analysis. L.W. (supporting): Resources. J.C. (supporting): Investigation. Y.T. (supporting): Validation. M.H. (supporting): Data curation. Y.L. (supporting): Visualization. K.T. (supporting): Project administration. L.L. (lead): Funding acquisition, Supervision, Writing – review & editing. H.J. (supporting): Supervision, Writing – review & editing. H.T. (supporting): Funding acquisition, Supervision, Writing – review & editing. All authors have read and approved the final version of the manuscript.
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This study was conducted in strict accordance with the Declaration of Helsinki and relevant Chinese ethical guidelines. The research protocol involving human samples was reviewed and approved by the Ethics Committee of Wanbei Coal-Electricity Group General Hospital (Approval No.: [WBZY-LLWYH-2022–001]).
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Qi, S., Chen, M., Ding, Z. et al. TET1 suppresses hepatocellular carcinoma progression by modulating the PI3K/Akt signaling pathways. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36334-3
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DOI: https://doi.org/10.1038/s41598-026-36334-3
