UBE2S and UBE2C confer a poor prognosis to breast cancer via downregulation of Numb.
UBE2S and UBE2C confer a poor prognosis to breast cancer via downregulation of Numb.
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DOI：
10.3389/fonc.2023.992233
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发表时间：
2023
影响因子：
4.7
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中科院分区：
文献类型：
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泛素结合酶E2 S（UBE 2S）和E2 C（UBE 2C）介导泛素化的生物学过程，已被广泛报道在各种癌症中。细胞命运决定因子和肿瘤抑制因子Numb也参与泛素化和蛋白酶体降解。然而，UBE 2S/UBE 2C和Numb之间的相互作用及其在乳腺癌（BC）临床结局中的作用尚未得到广泛阐明。 利用Oncomine、癌细胞系百科全书（CCLE）、人类蛋白质图谱（HPA）数据库、qRT-PCR和蛋白质印迹分析来分析各种癌症类型及其各自的正常对照、乳腺癌组织和乳腺癌细胞系中的UBE 2S/UBE 2C和Numb表达。比较UBE 2S、UBE 2C和Numb在不同ER、PR和HER 2状态、分级、分期和生存状态的BC患者中的表达。通过Kaplan-Meier检验进一步评估UBE 2S、UBE 2C和Numb在BC患者中的预后价值。我们还通过在BC细胞系中的过表达和敲低实验探索了UBE 2S/UBE 2C和Numb的潜在调控机制，并进行了生长和集落形成测定以评估细胞恶性度。在这项研究中，我们发现UBE 2S和UBE 2C在BC中过表达，而Numb在BC中下调，并且在更高级别，阶段和生存率低的BC中。与激素受体阴性（HR−）BC细胞系或组织相比，HR+ BC表现出较低的UBE 2S/UBE 2C和较高的Numb，对应于较好的存活率。我们还发现，UBE 2S/UBE 2C增加和Numb减少预测BC患者以及ER+ BC患者的预后不良。在BC细胞系中，UBE 2S/UBE 2C过表达降低Numb水平并增强细胞恶性度，而敲低UBE 2S/UBE 2C则表现出相反的效果。UBE 2S和UBE 2C下调Numb并增强BC恶性度。UBE 2S/UBE 2C和Numb的组合可能成为BC的新生物标志物。
Ubiquitin-conjugating enzymes E2S (UBE2S) and E2C (UBE2C), which mediate the biological process of ubiquitination, have been widely reported in various cancers. Numb, the cell fate determinant and tumor suppressor, was also involved in ubiquitination and proteasomal degradation. However, the interaction between UBE2S/UBE2C and Numb and their roles in the clinical outcome of breast cancer (BC) are not widely elucidated. Oncomine, Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) database, qRT-PCR, and Western blot analyses were utilized to analyze UBE2S/UBE2C and Numb expression in various cancer types and their respective normal controls, breast cancer tissues, and breast cancer cell lines. The expression of UBE2S, UBE2C, and Numb in BC patients with different ER, PR, and HER2 status, grades, stages, and survival status was compared. By Kaplan–Meier plotter, we further evaluated the prognostic value of UBE2S, UBE2C, and Numb in BC patients. We also explored the potential regulatory mechanisms underlying UBE2S/UBE2C and Numb through overexpression and knockdown experiments in BC cell lines and performed growth and colony formation assays to assess cell malignancy. In this study, we showed that UBE2S and UBE2C were overexpressed while Numb was downregulated in BC, and in BC of higher grade, stage, and poor survival. Compared to hormone receptor negative (HR−) BC cell lines or tissues, HR+ BC demonstrated lower UBE2S/UBE2C and higher Numb, corresponding to better survival. We also showed that increased UBE2S/UBE2C and reduced Numb predicted poor prognosis in BC patients, as well as in ER+ BC patients. In BC cell lines, UBE2S/UBE2C overexpression decreased the level of Numb and enhanced cell malignancy, while knocking down UBE2S/UBE2C demonstrated the opposite effects. UBE2S and UBE2C downregulated Numb and enhanced BC malignancy. The combination of UBE2S/UBE2C and Numb could potentially serve as novel biomarkers for BC.
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