Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.
Sci Rep. 2023 Oct 6;13(1):16899. doi: 10.1038/s41598-023-44189-1.
The biological functions of ubiquitin-conjugating enzymes E2 (UBE2) family members in uterine corpus endometrial carcinoma (UCEC) remains unclear. Our study aimed to systematically analyze the expression patterns, prognostic value, biological functions and molecular regulatory mechanisms of UBE2 family in UCEC. Among nine screened UBE2 family members associated with UCEC, UBE2C was the most significantly overexpressed gene with poor prognosis. High expression levels of UBE2C in UCEC was correlated with stages, histological subtypes, patient's menopause status and TP53 mutation. Three molecules (CDC20, PTTG1 and AURKA), were identified as the key co-expression proteins of UBE2C. The generic alterations (mutation, amplification) and DNA hypomethylation might contribute to UBE2C's high expression in UCEC. Furthermore, in vitro experiments showed that the interference of UBE2C inhibited the migration and invasion of endometrial cancer cells, while partially impact cell proliferation and didn't impact the expression of epithelial-mesenchymal transition (EMT) markers. Using comprehensive bioinformatics analysis and in vitro experiments, our study provided a novel insight into the oncogenic role of UBE2 family, specifically UBE2C in UCEC. UBE2C might serve as an effective biomarker to predict poor prognosis and a potential therapeutic target in clinical practice.
泛素结合酶 E2(UBE2)家族成员在子宫体子宫内膜癌(UCEC)中的生物学功能尚不清楚。本研究旨在系统分析 UBE2 家族在 UCEC 中的表达模式、预后价值、生物学功能和分子调控机制。在与 UCEC 相关的 9 个筛选出的 UBE2 家族成员中,UBE2C 是表达最显著上调且预后不良的基因。UBE2C 在 UCEC 中的高表达水平与分期、组织学亚型、患者绝经状态和 TP53 突变有关。鉴定出三个分子(CDC20、PTTG1 和 AURKA)作为 UBE2C 的关键共表达蛋白。泛素结合酶 E2(UBE2)家族成员在子宫体子宫内膜癌(UCEC)中的表达可能与基因的普遍改变(突变、扩增)和 DNA 低甲基化有关。此外,体外实验表明 UBE2C 的干扰抑制了子宫内膜癌细胞的迁移和侵袭,而对细胞增殖的影响较小,并且不影响上皮-间充质转化(EMT)标志物的表达。通过综合生物信息学分析和体外实验,本研究为 UBE2 家族,特别是 UBE2C 在 UCEC 中的致癌作用提供了新的见解。UBE2C 可能作为预测预后不良的有效生物标志物,并可能成为临床实践中的潜在治疗靶点。