Shi Yang, Wang Jiaxi, Cheng Qian, Wu Shuaihui, Qin Xian, Yang Zhiyong
Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China.
Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430071, China.
Mol Biol Rep. 2025 Jun 24;52(1):633. doi: 10.1007/s11033-025-10751-5.
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignancies worldwide. Ubiquitination is a biological process that regulates the degradation of proteins. Previous studies have indicated that ubiquitin ligase E3C (UBE3C) has procarcinogenic properties in various tumours. Nevertheless, the detailed role of UBE3C in PDAC is still unknown.
Bioinformatics analyses of UBE3C were performed, and we found that UBE3C expression was increased in PDAC cells and indicates a poorer clinical prognosis. Moreover, a significant positive correlation existed between UBE3C expression and the number of CD4 T cells in the tumour microenvironment (TME) of PDAC. CCK-8, colony formation, EdU and flow cytometry assays indicated that UBE3C knockdown promoted apoptosis and inhibited PDAC cell growth, whereas UBE3C overexpression had the opposite effects. Additionally, UBE3C catalysed p53 ubiquitination and promoted pancreatic carcinogenesis by facilitating p53 degradation. This effect was also confirmed in rescue experiments performed with pifithrin-α (PTF-α, an inhibitor of p53).
Our results clarify the importance of UBE3C in PDAC and indicate that the UBE3C-p53 axis may be a novel therapeutic target for PDAC.
Not applicable.
胰腺导管腺癌（PDAC）是全球最致命的恶性肿瘤之一。泛素化是一种调节蛋白质降解的生物学过程。先前的研究表明，泛素连接酶E3C（UBE3C）在各种肿瘤中具有促癌特性。然而，UBE3C在PDAC中的具体作用仍不清楚。
对UBE3C进行了生物信息学分析，我们发现UBE3C在PDAC细胞中的表达增加，并且提示临床预后较差。此外，在PDAC的肿瘤微环境（TME）中，UBE3C表达与CD4 T细胞数量之间存在显著正相关。CCK-8、集落形成、EdU和流式细胞术分析表明，敲低UBE3C可促进细胞凋亡并抑制PDAC细胞生长，而UBE3C过表达则产生相反的效果。此外，UBE3C催化p53泛素化，并通过促进p53降解来促进胰腺癌发生。在用pifithrin-α（PTF-α，一种p53抑制剂）进行的挽救实验中也证实了这种作用。
我们的结果阐明了UBE3C在PDAC中的重要性，并表明UBE3C-p53轴可能是PDAC的一个新的治疗靶点。
不适用。
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