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

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-09-12 DOI:10.1016/j.cellsig.2025.112131

Song Huang , Yuehong Cai , Xueqing Zhao , Xiaohong Du , Haijun Hu

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引用次数: 0

Abstract

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.

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肝细胞癌中P4HB表达升高及其在uca1介导的恶性进展中的作用

肝细胞癌（HCC）是全球癌症相关死亡的主要原因，强调了改进诊断和治疗策略的迫切需要。在这项研究中，我们研究了脯氨酸4-羟化酶亚基β (P4HB)在HCC进展中的作用及其作为诊断生物标志物的潜力。单细胞测序分析显示P4HB在恶性HCC细胞群中高表达。血清分析显示，与健康对照组和良性肝病患者相比，HCC患者的P4HB水平显著升高，ROC分析显示，HCC患者的P4HB水平具有较高的诊断性能，特别是与甲胎蛋白（AFP）联合使用时。体外和体内功能实验证实，P4HB促进HCC细胞的增殖、迁移和侵袭。此外，我们发现了P4HB和lncRNA UCA1之间的一种新的相互作用，这种相互作用增强了HCC细胞中的糖酵解和恶性行为。这些发现表明，P4HB是HCC诊断的有希望的生物标志物和潜在的治疗靶点，特别是在其与UCA1相互作用的背景下。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.