TY  - EJOU
AU  - JIANG, DONG 
AU  - QI, ZHI 
AU  - XU, ZHIYING 
AU  - LI, YIRAN 

TI  - <i>CYB5D2</i> inhibits the malignant progression of hepatocellular carcinoma by inhibiting <i>TGF-β</i> expression and epithelial-mesenchymal transition
T2  - Oncology Research

PY  - 2025
VL  - 33
IS  - 3
SN  - 1555-3906

AB  -  <b>Background:</b> Hepatocellular carcinoma (HCC) is a prevalent liver malignancy. This study examined the roles of transforming growth factor beta (<i>TGF-β</i>) and cytochrome b5 domain containing 2 (<i>CYB5D2</i>) in HCC etiology and their prognostic biomarker potential. <b>Methods:</b> 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 <i>CYB5D2</i> and <i>TGF-β</i> in HCC cell lines were quantified using Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB) assays. Effects of <i>CYB5D2</i> overexpression on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) marker regulation were assessed <i>in vitro</i>, while <i>in vivo</i> tumorigenicity was evaluated using a xenograft model of HCC in nude mice. <b>Results:</b> 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 <i>CYB5D2</i> being underexpressed in HCC cells and tissues. <i>TGF-β</i> was negatively correlated with <i>CYB5D2</i> expression, resulting in poor patient prognosis. Functional assays demonstrated that <i>CYB5D2</i> overexpression inhibited proliferation, migration, and invasion of HCC cell lines, and altered EMT marker expression. Furthermore, the addition of <i>TGF-β</i> partially reversed the suppressive effects caused by <i>CYB5D2</i> overexpression. <i>In vivo</i>, CYB5D2 overexpression significantly reduced tumor growth, indicating its potential as a therapeutic target for HCC. <b>Conclusion:</b> The tumor suppressor function of <i>CYB5D2</i> in HCC and its interaction with <i>TGF-β</i> offered fresh information on the molecular pathophysiology of HCC and possible treatment avenues.
KW  - Cytochrome b5 domain containing 2 <b>(</b><i>CYB5D2</i>); Malignant progression; Hepatocellular carcinoma (HCC); Transforming growth factor beta (<i>TGF-β</i>); Epithelial-mesenchymal transition (EMT)

DO  - 10.32604/or.2024.050125