Research Paper Volume 12, Issue 11 pp 10275—10289
UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT
- 1 Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing 100021, China
- 2 State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Received: January 17, 2020 Accepted: March 31, 2020 Published: June 3, 2020
https://doi.org/10.18632/aging.103239How to Cite
Copyright © 2020 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.
Abbreviations
GBM: glioblastoma; UBE2T: Ubiquitin-conjugating enzyme E2T; GRP78: Endoplasmic Reticulum Lumenal Ca (2+)-Binding Protein Grp78; EMT: epithelial-mesenchymal transition; TMZ: temozolomide; CGGA: the Chinese Glioma Genome Atlas; GTEx: the Genotype-Tissue Expression Project; DEGs: differentially expressed genes; IHC: immunohistochemistry; IB: Immunoblotting; IP: immunoprecipitation.