Elevated P4HB expression in hepatocellular carcinoma and its role in UCA1-mediated malignant progression

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, underscoring the urgent need for improved diagnostic and therapeutic strategies. In this study, we investigated the role of Prolyl 4-hydroxylase subunit beta (P4HB) in HCC progression and its potential as a diagnostic biomarker. Single-cell sequencing analysis revealed that P4HB is highly expressed in malignant HCC cell populations. Serum analysis demonstrated that P4HB levels were significantly elevated in HCC patients compared to healthy controls and those with benign liver diseases, with ROC analysis showing a high diagnostic performance, particularly when combined with alpha-fetoprotein (AFP). Functional assays, both in vitro and in vivo, confirmed that P4HB promotes the proliferation, migration, and invasion of HCC cells. Furthermore, we identified a novel interaction between P4HB and the lncRNA UCA1, which enhances glycolysis and malignant behavior in HCC cells. These findings suggest that P4HB is a promising biomarker for HCC diagnosis and a potential therapeutic target, particularly in the context of its interaction with UCA1.