Zhang Qianshi, Zhang Yinan, Sun Zhiwei, Wang Huanle, Dai Guohang, Meng Yue, Shi Shasha, Ren Shuangyi
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Clinical Laboratory, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Front Oncol. 2025 May 8;15:1581860. doi: 10.3389/fonc.2025.1581860. eCollection 2025.
P4HA2 is implicated in regulating tumor microenvironment formation and may play roles in inflammation and tumor immunity. However, its mechanistic involvement in colorectal cancer (CRC) remains largely unexplored.
We analyzed P4HA2 expression in CRC tissues and correlated it with clinicopathological features. Functional assays (CCK8, wound healing, Transwell) were performed to assess proliferation and migration. Proteomic analysis identified downstream targets, with STAT1/PD-L1 pathway validation.
High P4HA2 expression correlated with advanced T/M stages and served as an independent poor prognostic factor. Functional experiments confirmed P4HA2's role in promoting CRC proliferation and migration. Mechanistically, P4HA2 bound to and downregulated STAT1, subsequently modulating the STAT1/PD-L1 pathway.
Our findings reveal P4HA2 promotes CRC progression and suppresses anti-tumor immunity via STAT1/PD-L1 axis regulation. This study uncovers a novel pathogenic mechanism, positioning P4HA2 as a potential therapeutic target in CRC.
P4HA2参与调节肿瘤微环境的形成,可能在炎症和肿瘤免疫中发挥作用。然而,其在结直肠癌(CRC)中的作用机制在很大程度上仍未得到探索。
我们分析了CRC组织中P4HA2的表达,并将其与临床病理特征相关联。进行了功能试验(CCK8、伤口愈合、Transwell)以评估增殖和迁移。蛋白质组学分析确定了下游靶点,并对STAT1/PD-L1途径进行了验证。
P4HA2高表达与晚期T/M分期相关,是独立的不良预后因素。功能实验证实了P4HA2在促进CRC增殖和迁移中的作用。机制上,P4HA2与STAT1结合并使其下调,随后调节STAT1/PD-L1途径。
我们的研究结果表明,P4HA2通过调节STAT1/PD-L1轴促进CRC进展并抑制抗肿瘤免疫。本研究揭示了一种新的致病机制,将P4HA2定位为CRC的潜在治疗靶点。