Open Access
ARTICLE
CYB5D2 inhibits the malignant progression of hepatocellular carcinoma by inhibiting TGF-β expression and epithelialmesenchymal transition
DONG JIANG1, ZHI QI3, ZHIYING XU2,*, YIRAN LI1,*
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
* Address correspondence to: Zhiying Xu, zyxu_xinling@sina.com;
Yiran Li, liyiranehsh@sina.com
Oncology Research https://doi.org/10.32604/or.2024.050125
Received 28 January 2024; Accepted 19 June 2024; Published online 15 July 2024
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.
Keywords
Cytochrome b5 domain containing 2 (CYB5D2), Malignant progression, Hepatocellular carcinoma (HCC), Transforming growth factor beta (TGF-β), Epithelial-mesenchymal transition (EMT)
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