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BEND3 promotes hepatocellular carcinoma progression and metastasis by activating the PI3K/AKT/mTOR pathway and inducing epithelial-mesenchymal transition - 29/03/25

Doi : 10.1016/j.clinre.2025.102582 
Liu-lin Yang 1, Xing Chen 2, Kai-ting Huang 1, Shao-tong Tang 1, Gui-yan Ye 1, Ji-long Wang 1,
1 Department of Hepatological Surgery, Guangxi Medical University First Affiliated Hospital, China 
2 Department of Ultrasonography, Guangxi Medical University First Affiliated Hospital, China 

Corresponding author.
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Highlights

Innovation 1: First identification of the functional role of BEND3 in HCC. This study is the first to elucidate the critical role of BEND3 in the progression and metastasis of hepatocellular carcinoma (HCC), addressing the gap in research on the BEND family in HCC and advancing our understanding of the molecular mechanisms underlying HCC.
Innovation 2: Discovery of a novel mechanism by which BEND3 regulates the PI3K/AKT/mTOR signaling pathway. The study reveals that BEND3 promotes HCC cell proliferation, invasion, and metastasis by activating the PI3K/AKT/mTOR signaling pathway, providing new insights into the regulation of this key pathway.
Innovation 3: Elucidation of the mechanism by which BEND3 induces epithelial-mesenchymal transition (EMT). For the first time, this study demonstrates that BEND3 induces epithelial-mesenchymal transition (EMT) via the PI3K/AKT/mTOR signaling pathway, enhancing the invasive and metastatic capabilities of HCC cells and contributing new theoretical insights to the field of EMT research.
Innovation 4: Quantification of BEND3 expression in multiple clinical samples and its relevance for clinical applications. By analyzing BEND3 expression levels in multiple clinical HCC samples, this study identifies a significant upregulation of BEND3 in tumor tissues and establishes its association with poor patient prognosis. These findings support the potential use of BEND3 as a diagnostic biomarker and prognostic tool for HCC, highlighting its translational value in clinical applications.

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Abstract

Objective

This study aimed to investigate the expression of BEND3 in hepatocellular carcinoma (HCC), its correlation with clinical characteristics, and its functional and mechanistic impacts on HCC progression.

Methods

Bioinformatics analyses identified BEND3 as highly expressed in HCC and associated with poor clinical prognosis, which was further validated using qRT-PCR, western blotting and immunohistochemistry. Stable BEND3-overexpressing and silenced cell lines were constructed to evaluate its functional effects. CCK-8 and colony formation assays assessed its influence on cell proliferation, while wound healing and Transwell assays evaluated its role in migration and invasion. WB and immunofluorescence were employed to analyze the effects of BEND3 on epithelial-mesenchymal transition (EMT) and the PI3K/AKT/mTOR signaling pathway.

Results

Public database analysis, alongside qRT-PCR, western blotting, and immunohistochemical, confirmed that BEND3 expression is significantly elevated in HCC tissues compared to normal liver tissues and is closely associated with poor prognosis. Functional assays demonstrated that BEND3 promotes HCC cell proliferation, migration, and invasion. Mechanistic studies revealed that BEND3 drives HCC progression by inducing EMT and activating the PI3K/AKT/mTOR signaling pathway.

Conclusion

BEND3 is highly expressed in HCC and strongly correlates with poor clinical outcomes. Functional and mechanistic analyses indicate that BEND3 enhances HCC progression by promoting proliferation, migration and invasion via EMT induction and PI3K/AKT/mTOR pathway activation.

Le texte complet de cet article est disponible en PDF.

Keywords : BEND3, hepatocellular carcinoma, proliferation and migration, EMT, PI3K/AKT/mTOR


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