Zhang Ping, Guo Huiping, Zhao Fang, Jia Ke, Yang Fei, Liu Xiaoli
Department of Gynaecology, The First People's Hospital of Zhangjiagang Affiliated to Suzhou University, No. 68, West Jiyang Road, Zhangjiagang 215600, Jiangsu, China.
Department of Gynaecology, The First People's Hospital of Zhangjiagang Affiliated to Suzhou University, Zhangjiagang 215600, Jiangsu, China.
Open Med (Wars). 2023 Feb 24;18(1):20220567. doi: 10.1515/med-2022-0567. eCollection 2023.
Emerging evidence has demonstrated that ubiquitin conjugating enzyme E2 J1 (UBE2J1) exerts pivotal function in many cancers. UBE2J1 was reported to be dysregulated in endometrial cancer (EC). This study was designed to further investigate the regulatory character and mechanism of UBE2J1 in EC. Bioinformatic tools and databases were used to analyze gene expression pattern and gene expression correlation in EC tissues, and the prognosis of EC patients. Gene expression was evaluated by reverse-transcription quantitative polymerase chain reaction. Western blot was used for protein level detection. cell apoptosis was detected by flow cytometry analyses and TUNEL assays. cell apoptosis was evaluated by detecting Bax and Bcl-2 expression in tumor tissues via immunohistochemical and western blot analyses. In this study, UBE2J1 knockdown promoted cell apoptosis in EC cells and in mouse models of EC. PI3K and AKT expression is positively correlated with UBE2J1 level and is related to poor prognosis of EC patients. UBE2J1 knockdown repressed the PI3K/AKT pathway both and . UBE2J1 downregulation decreased MDM2 expression, but increased p53 expression. MDM2 overexpression reverses the promotion of UBE2J1 knockdown on cell apoptosis in EC. Overall, UBE2J1 knockdown induces cell apoptosis in EC by inactivating the PI3K/AKT signaling and suppressing the MDM2/p53 signaling.
新出现的证据表明，泛素结合酶E2 J1（UBE2J1）在许多癌症中发挥着关键作用。据报道，UBE2J1在子宫内膜癌（EC）中表达失调。本研究旨在进一步探讨UBE2J1在EC中的调控特征及机制。利用生物信息学工具和数据库分析EC组织中的基因表达模式、基因表达相关性以及EC患者的预后。通过逆转录定量聚合酶链反应评估基因表达。蛋白质印迹法用于检测蛋白质水平。通过流式细胞术分析和TUNEL检测法检测细胞凋亡。通过免疫组织化学和蛋白质印迹分析检测肿瘤组织中Bax和Bcl-2的表达来评估细胞凋亡。在本研究中，UBE2J1基因敲低促进了EC细胞和EC小鼠模型中的细胞凋亡。PI3K和AKT的表达与UBE2J1水平呈正相关，并且与EC患者的不良预后相关。UBE2J1基因敲低在体内和体外均抑制了PI3K/AKT信号通路。UBE2J1下调降低了MDM2的表达，但增加了p53的表达。MDM2过表达逆转了UBE2J1基因敲低对EC细胞凋亡的促进作用。总体而言，UBE2J1基因敲低通过使PI3K/AKT信号失活和抑制MDM2/p53信号来诱导EC细胞凋亡。
