UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT
UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT
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UBE2T 通过稳定 GRP78 和调节 EMT 促进胶质母细胞瘤侵袭和迁移
DOI：
10.18632/aging.103239
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发表时间：
2020-06-15
期刊：
影响因子：
5.2
通讯作者：
Song, Yongmei
中科院分区：
文献类型：
--
作者：
Huang, Peng;Guo, Yuduo;Song, Yongmei
胶质母细胞瘤（GBM）通常预后不佳，随着疾病的进展，它与生活质量差有关。然而，GBM的有效治疗方法的发展一直不足。泛素偶联酶E2T （UBE2T）是泛素-蛋白酶体途径E2家族的成员，是肿瘤进展的重要调节因子，但其在GBM中的作用尚不清楚。在本研究中，我们旨在阐明UBE2T在GBM中的作用。生物信息学分析确定UBE2T是胶质瘤的独立危险因素。采用免疫组织化学方法检测UBE2T在GBM患者和正常组织样本中的表达。采用Transwell法分析UBE2T对GBM细胞侵袭和迁移的影响。体内实验采用BALB/c裸鼠。采用免疫印迹法和免疫沉淀法确定其分子机制。UBE2T在GBM组织中高表达，其表达与预后不良有关。在体外，UBE2T的缺失显著抑制了细胞的侵袭和迁移。此外，UBE2T缺失在体内抑制GBM皮下肿瘤的生长。进一步的实验表明，UBE2T通过稳定GRP78调节GBM细胞的上皮-间质转化（EMT）来抑制侵袭和迁移。我们发现了一个新的UBE2T/GRP78/EMT调控轴，它调节GBM的恶性进展和复发，表明该轴可能是一个有价值的治疗靶点。
Glioblastoma (GBM) generally has a dismal prognosis, and it is associated with a poor quality of life as the disease progresses. However, the development of effective therapies for GBM has been deficient. Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the E2 family in the ubiquitin-proteasome pathway and a vital regulator of tumour progression, but its role in GBM is unclear. In this study, we aimed to clarify the role of UBE2T in GBM. Bioinformatics analysis identified UBE2T as an independent risk factor for gliomas. Immunohistochemistry was used to measure UBE2T expression in GBM and normal tissue samples obtained from patients with GBM. The effects of UBE2T on GBM cell invasion and migration were analysed using the Transwell assay. BALB/c nude mice were used for the in vivo assays. Immunoblotting and immunoprecipitation were performed to determine the molecular mechanisms. UBE2T was highly expressed in GBM tissues, and its expression was linked to a poor prognosis. In vitro, depletion of UBE2T significantly suppressed cell invasion and migration. Moreover, UBE2T depletion suppressed the growth of GBM subcutaneous tumours in vivo. Further experiments revealed that UBE2T suppressed invasion and migration by regulating epithelial-mesenchymal transition (EMT) via stabilising GRP78 in GBM cells. We uncovered a novel UBE2T/GRP78/EMT regulatory axis that modulates the malignant progression and recurrence of GBM, indicating that the axis might be a valuable therapeutic target.