Abstract

Purpose

Breast cancer (BCa) is one of the most common gynecological malignancies. Ubiquitin-coupled enzyme E2T (UBE2T) has been demonstrated to play crucial roles in various tumors.

Methods

UBE2T levels were detected using quantitative real time PCR and western blot. CCK-8 and colony formation assays were used to evaluate cell proliferation. A xenograft model was used to evaluate the effects of UBE2T on tumor growth in mice, and immunohistochemistry (IHC) assay was performed to detect the expression of UBE2T and Ki-67. Transwell assay was performed to determine cell migration and invasion. The ATP level, glucose consumption and lactate production were measured using the corresponding commercial kits. Western blot assay was used to detect the levels of epithelial-mesenchymal transformation (EMT), glycolytic and the PI3K/AKT pathway related proteins regulated by UBE2T.

Results

Upregulation of UBE2T expression in human BCa tissues was found in human clinical BCa tissues and The Cancer Genome Atlas (TCGA) dataset. The expression of UBE2T was confirmed to be up-regulated in BCa cells compared to normal breast epithelial cell line (MCF-10A). Overexpression of UBE2T promoted proliferation, migration, invasion and glycolysis in BCa cells, while UBE2T knockdown showed the opposite results. Moreover, UBE2T knockdown suppressed tumor growth in mice. Further mechanism analysis shows that UBE2T participated in the regulation of BCa progression through affecting the PI3K/AKT signaling pathway.

Conclusion

UBE2T promoted proliferation, invasion and glycolysis through modulating PI3K/AKT signaling pathway in BCa, implying that UBE2T may provide a promising therapeutic target for the therapy of BCa.

中文翻译：

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UBE2T通过调节PI3K / AKT信号通路促进乳腺癌细胞的增殖，侵袭和糖酵解

摘要

目的

乳腺癌（BCa）是最常见的妇科恶性肿瘤之一。泛素偶联酶E2T（UBE2T）已被证明在各种肿瘤中起关键作用。

方法

使用定量实时PCR和western blot检测UBE2T水平。使用CCK-8和集落形成测定法来评估细胞增殖。使用异种移植模型评估UBE2T对小鼠肿瘤生长的影响，并进行免疫组织化学（IHC）分析以检测UBE2T和Ki-67的表达。进行Transwell测定以确定细胞迁移和侵袭。使用相应的商业套件测量ATP水平，葡萄糖消耗和乳酸产生。蛋白质印迹法用于检测UBE2T调控的上皮-间质转化（EMT），糖酵解和PI3K / AKT途径相关蛋白的水平。

结果

在人临床BCa组织和癌症基因组图谱（TCGA）数据集中发现了人BCa组织中UBE2T表达的上调。与正常乳腺上皮细胞系（MCF-10A）相比，证实BCA细胞中UBE2T的表达上调。UBE2T的过表达促进了BCa细胞的增殖，迁移，侵袭和糖酵解，而UBE2T的敲低则相反。此外，UBE2T组合式抑制小鼠肿瘤的生长。进一步的机理分析表明，UBE2T通过影响PI3K / AKT信号通路参与了BCa进程的调控。

结论

UBE2T通过调节BCa中的PI3K / AKT信号传导途径促进增殖，侵袭和糖酵解，这表明UBE2T可能为BCa的治疗提供有希望的治疗靶点。