Qingdao Medical College, Qingdao University, Qingdao, Shandong 266071, P.R. China.
The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China.
Int J Oncol. 2023 Apr;62(4). doi: 10.3892/ijo.2023.5500. Epub 2023 Mar 10.
Pancreatic ductal adenocarcinoma (PDAC) is a noteworthy malignant carcinoma with an unsatisfactory prognosis attributed to late diagnosis. Ubiquitin‑conjugating enzyme E2K (UBE2K) has been found to serve important roles in a number of diseases. However, its function and the exact molecular mechanism of UBE2K in PDAC remain to be elucidated. The present study discovered that UBE2K was expressed at high levels and indicated the poor prognosis of patients with PDAC. Following this, the CCK‑8, colony formation, and sphere formation assays showed that UBE2K promoted proliferation and the stemness phenotype of PDAC cells . Evidence from subcutaneous tumor‑bearing nude mice experiments further confirmed that UBE2K enhanced PDAC cell tumorigenesis . Additionally, the present study demonstrated that insulin‑like growth factor 2 RNA binding protein 3 (IGF2BP3) functioned as an RNA‑binding protein to increase UBE2K expression by enhancing the RNA stability of UBE2K. The knockdown or overexpression of IGF2BP3 could attenuate the change in cells growth induced by the overexpression or knockdown of UBE2K. In summary, the findings indicated the oncogenic roles of UBE2K in PDAC. In addition, IGF2BP3 and UBE2K constitute a functional axis to regulate the malignant progression of PDAC.
胰腺导管腺癌（PDAC）是一种显著的恶性癌，由于诊断较晚，预后不佳。泛素结合酶 E2K（UBE2K）在许多疾病中发挥着重要作用。然而，UBE2K 在 PDAC 中的功能及其确切的分子机制仍有待阐明。本研究发现 UBE2K 表达水平较高，提示 PDAC 患者预后不良。随后，CCK-8、集落形成和球体形成试验表明 UBE2K 促进了 PDAC 细胞的增殖和干性表型。来自皮下荷瘤裸鼠实验的证据进一步证实，UBE2K 增强了 PDAC 细胞的肿瘤发生。此外，本研究表明胰岛素样生长因子 2 RNA 结合蛋白 3（IGF2BP3）作为一种 RNA 结合蛋白，通过增强 UBE2K 的 RNA 稳定性来增加 UBE2K 的表达。IGF2BP3 的敲低或过表达可以减弱 UBE2K 的过表达或敲低引起的细胞生长变化。综上所述，这些发现表明 UBE2K 在 PDAC 中具有致癌作用。此外，IGF2BP3 和 UBE2K 构成了一个功能轴，调节 PDAC 的恶性进展。
