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

Abstract

Aim Hepatocellular carcinoma (HCC) is a common liver malignancy. In this study, our goal was to investigate how TGF-β and CYB5D2 function in the etiology of HCC and their potential as prognostic biomarkers. Methods Gene co-expression network and prognostic analysis were executed on the GSE101685 dataset, and CYB5D2 was determined to be a hub gene. Then the expression of CYB5D2 and TGF-β in HCC and their correlation were detected. In vitro experiments analyzed the effects of CYB5D2 and TGF-β on the progression of HCC. Tumor xenograft experiments were performed to detect the regulation of CYB5D2 overexpression on tumor growth. Results Immunohistochemistry (IHC) and expression analysis results showed that CYB5D2 can serve as a tumor suppressor in HCC. In contrast, TGF-β, which is inversely correlated with CYB5D2, was overexpressed in liver hepatocellular carcinoma (LIHC) and linked to poor patient prognosis. In vitro experiments confirmed that CYB5D2 expression was upregulated in HCC cell lines, while TGF-β expression was upregulated, and results from the Human Protein Atlas (HPA) database confirmed these findings. Functional analysis showed that CYB5D2 overexpression inhibited the proliferation, migration, and invasion of HCC cells and induced G1 phase arrest. Furthermore, TGF-β treatment counteracted CYB5D2-mediated epithelial-mesenchymal transition (EMT) marker expression and tumor progression. Finally, in vivo studies showed that CYB5D2 overexpression significantly reduced tumor growth, suggesting its potential anticancer activity against HCC. Conclusion Overall, the tumor suppressor function of CYB5D2 in HCC and its interaction with TGF-β offer fresh information on the molecular pathophysiology of HCC and possible treatment avenues.