Department of Hematology, Affiliated Hangzhou First People's Hospital, West Lake University, School of Medicine, Hangzhou, China.
Team of neonatal & infant development, health and nutrition, NDHN. School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China.
J Cell Mol Med. 2024 Aug;28(16):e70037. doi: 10.1111/jcmm.70037.
Ubiquitin like modifier activating enzyme 1 (UBA1) plays an important role in immune regulation and cellular function. However, the functional mechanism and role of UBA1 in pan-cancer have not been fully elucidated and its value in haematological tumours (diffuse large B cell lymphoma (DLBC/DLBCL) and acute myeloid leukaemia (AML/LAML)) has not been explored. We conducted a comprehensive analysis of the functional mechanism and role of UBA1 in pan-cancer using multiple databases, including differential expression analysis, clinical pathological staging analysis, prognosis analysis and immune analysis. Then, we confirmed the function of UBA1 in haematological tumours through cell experiments. The results showed that the expression of UBA1 was significantly increased in most cancers and the differential expression of UBA1 was mainly concentrated in digestive tumours, haematological tumours and brain tumours. Moreover, the high expression of UBA1 had poor prognosis in most tumours, which may be related to its involvement in various cancer-related pathways such as cell cycle, as well as its methylation level, protein phosphorylation level, immune cell infiltration and immune therapy response. Cell experiments have confirmed that UBA1 can significantly regulate the cycle progression and apoptosis of DLBCL cells and AML cells. Therefore, UBA1 may be a potential therapeutic target for haematological tumours. In summary, our study not only comprehensively analysed the functional mechanisms and clinical value of UBA1 in pan-cancer, but also validated for the first time the regulatory role of UBA1 in haematological tumours.
泛癌中泛素样修饰酶激活酶 1(UBA1)在免疫调节和细胞功能中发挥着重要作用。然而,UBA1 在泛癌中的功能机制和作用尚未完全阐明,其在血液肿瘤(弥漫性大 B 细胞淋巴瘤(DLBC/DLBCL)和急性髓系白血病(AML/LAML))中的价值尚未被探索。我们使用多个数据库(包括差异表达分析、临床病理分期分析、预后分析和免疫分析)对 UBA1 在泛癌中的功能机制和作用进行了全面分析。然后,我们通过细胞实验证实了 UBA1 在血液肿瘤中的功能。结果表明,UBA1 在大多数癌症中的表达明显增加,UBA1 的差异表达主要集中在消化肿瘤、血液肿瘤和脑肿瘤中。此外,UBA1 的高表达在大多数肿瘤中预后不良,这可能与其参与细胞周期等多种癌症相关途径以及其甲基化水平、蛋白磷酸化水平、免疫细胞浸润和免疫治疗反应有关。细胞实验已经证实,UBA1 可以显著调节 DLBCL 细胞和 AML 细胞的周期进程和凋亡。因此,UBA1 可能是血液肿瘤的潜在治疗靶点。综上所述,本研究不仅全面分析了 UBA1 在泛癌中的功能机制和临床价值,还首次验证了 UBA1 在血液肿瘤中的调节作用。