Open Access

ARTICLE

CYB5D2 inhibits the malignant progression of hepatocellular carcinoma by inhibiting TGF-β expression and epithelial-mesenchymal transition

DONG JIANG¹, ZHI QI³, ZHIYING XU^2,*, YIRAN LI^1,*

1 Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, China
2 Department of Hepatic Surgery IV, Shanghai Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, China
3 Department of Neurology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, China

* Corresponding Authors: ZHIYING XU. Email: ; YIRAN LI. Email:

Oncology Research 2025, 33(3), 709-722. https://doi.org/10.32604/or.2024.050125

Received 28 January 2024; Accepted 19 June 2024; Issue published 28 February 2025

Abstract

Background: Hepatocellular carcinoma (HCC) is a prevalent liver malignancy. This study examined the roles of transforming growth factor beta (TGF-β) and cytochrome b5 domain containing 2 (CYB5D2) in HCC etiology and their prognostic biomarker potential. Methods: Key modules and prognostic genes were identified by analyzing the GSE101685 dataset by weighted gene co-expression network analysis (WGCNA) and Least absolute shrinkage and selection operator (LASSO) Cox regression. The expression levels of CYB5D2 and TGF-β in HCC cell lines were quantified using Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB) assays. Effects of CYB5D2 overexpression on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) marker regulation were assessed in vitro, while in vivo tumorigenicity was evaluated using a xenograft model of HCC in nude mice. Results: In this study, WGCNA identified the turquoise module as significantly associated with HCC, containing 452 DEGs. LASSO Cox regression analysis revealed 9 key prognostic genes, with CYB5D2 being underexpressed in HCC cells and tissues. TGF-β was negatively correlated with CYB5D2 expression, resulting in poor patient prognosis. Functional assays demonstrated that CYB5D2 overexpression inhibited proliferation, migration, and invasion of HCC cell lines, and altered EMT marker expression. Furthermore, the addition of TGF-β partially reversed the suppressive effects caused by CYB5D2 overexpression. In vivo, CYB5D2 overexpression significantly reduced tumor growth, indicating its potential as a therapeutic target for HCC. Conclusion: The tumor suppressor function of CYB5D2 in HCC and its interaction with TGF-β offered fresh information on the molecular pathophysiology of HCC and possible treatment avenues.

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Supplementary Material

Supplementary Material File

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