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TRIM29 modulates proteins involved in PTEN/AKT/mTOR and JAK2/STAT3 signaling pathway and suppresses the progression of hepatocellular carcinoma

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Abstract

Tripartite motif–containing 29 (TRIM29), also known as the ataxia telangiectasia group D-complementing (ATDC) gene, has been reported to play an oncogenic or tumor suppressive role in developing different tumors. So far, its expression and biological functions in hepatocellular carcinoma (HCC) remain unclear. We investigated TRIM29 expression pattern in human HCC samples using quantitative RT-PCR and immunohistochemistry. Relationships between TRIM29 expression level, clinical prognostic indicators, overall survival (OS), and disease-free survival (DFS) were evaluated by Kaplan–Meier analysis and Cox proportional hazards model. A series of in vitro experiments and a xenograft tumor model were conducted to detect the functions of TRIM29 in HCC cells. RNA sequencing, western blotting, and immunochemical staining were performed to assess the molecular regulation of TRIM29 in HCC. We found that the mRNA and protein levels of TRIM29 were significantly reduced in HCC samples, compared with adjacent noncancerous tissues, and were negatively correlated with poor differentiation of HCC tissues. Survival analysis confirmed that lower TRIM29 expression significantly correlated with shorter OS and DFS of HCC patients. TRIM29 overexpression remarkably inhibited cell proliferation, migration, and EMT in HCC cells, whereas knockdown of TRIM29 reversed these effects. Moreover, deactivation of the PTEN/AKT/mTOR and JAK2/STAT3 pathways might be involved in the tumor suppressive role of TRIM29 in HCC. Our findings indicate that TRIM29 in HCC exerts its tumor suppressive effects through inhibition of the PTEN/AKT/mTOR and JAK2/STAT3 signaling pathways and may be used as a potential biomarker for survival in patients with HCC.

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The data and materials used in this research are available from the corresponding author upon reasonable request.

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Acknowledgements

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Funding

This work was funded by the National Nature Science Foundation of China (Project No. 81772884 and 81772991).

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  1. Yu-Ting Yin, Lu Shi, and Chun Wu have contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China

    Yu-Ting Yin, Lu Shi, Chun Wu, Mei-Yin Zhang, Jia-Xin Li, Yu-Feng Zhou, Shuo-Cheng Wang, Hui-Yun Wang & Shi-Juan Mai

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Contributions

YTY performed the main experiments and wrote the manuscript. LS, CW, MYZ, JXL, YFZ and SCW assisted with all experiments. HYW and SJM designed the project. All authors have read and approved the final manuscript.

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Correspondence to Hui-Yun Wang or Shi-Juan Mai.

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The author declares that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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All animal experiments were performed according to the Animal Ethics Procedures and approved by the Sun Yat-Sen University Animal Ethics Committee. The Institutional Review Board of Sun Yat-Sen University Cancer Center approved this study. Reference number: L102012017004C.

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Supplementary Fig. 1

TRIM29 overexpression inhibits EMT and mTOR signaling pathways in Bel-7402 cells.

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Supplementary file2 (TIF 2214 KB)

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Yin, YT., Shi, L., Wu, C. et al. TRIM29 modulates proteins involved in PTEN/AKT/mTOR and JAK2/STAT3 signaling pathway and suppresses the progression of hepatocellular carcinoma. Med Oncol 41, 79 (2024). https://doi.org/10.1007/s12032-024-02307-7

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