Receptor-Interacting Protein 140 Enhanced Temozolomide-Induced Cellular Apoptosis Through Regulation of E2F1 in Human Glioma Cell Lines.

Autor: Tsai HC; Department of Neurosurgery, Linkou Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.; Graduate Institute of Clinical Medical Sciences and School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 333, Taiwan., Wei KC; Department of Neurosurgery, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital, New Taipei Municipal, Taipei, 236, Taiwan.; Department of Neurosurgery, Keelung Chang Gung Memorial Hospital, Keelung, 204, Taiwan., Chen PY; Department of Neurosurgery, Keelung Chang Gung Memorial Hospital, Keelung, 204, Taiwan.; School of Medicine, Chang Gung University, Taoyuan, 333, Taiwan., Huang CY; Department of Neurosurgery, Linkou Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.; School of Medicine, Chang Gung University, Taoyuan, 333, Taiwan., Chen KT; Department of Neurosurgery, Linkou Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.; School of Medicine, Chang Gung University, Taoyuan, 333, Taiwan., Lin YJ; Department of Neurosurgery, Linkou Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.; School of Medicine, Chang Gung University, Taoyuan, 333, Taiwan., Cheng HW; Department of Neurosurgery, Linkou Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.; Department of Pharmacology, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan.; Department of Pharmacology, National Yang-Ming University, Taipei, 112, Taiwan., Huang CH; Department of Pharmacology, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan., Wang HT; Department of Pharmacology, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan. htwang01@nycu.edu.tw.; Department of Pharmacology, National Yang-Ming University, Taipei, 112, Taiwan. htwang01@nycu.edu.tw.
Jazyk: angličtina
Zdroj: Neuromolecular medicine [Neuromolecular Med] 2022 Jun; Vol. 24 (2), pp. 113-124. Date of Electronic Publication: 2021 Jun 01.
DOI: 10.1007/s12017-021-08667-x
Abstrakt: Glioblastoma (GBM), a grade IV glioma, is responsible for the highest years of potential life lost among cancers. The poor prognosis is attributable to its high recurrence rate, caused in part by the development of resistance to chemotherapy. Receptor-interacting protein 140 (RIP140) is a very versatile coregulator of nuclear receptors and transcription factors. Although many of the pathways regulated by RIP140 contribute significantly to cancer progression, the function of RIP140 in GBM remains to be determined. In this study, we found that higher RIP140 expression was associated with prolonged survival in patients with newly diagnosed GBM. Intracellular RIP140 levels were increased after E2F1 activation following temozolomide (TMZ) treatment, which in turn modulated the expression of E2F1-targeted apoptosis-related genes. Overexpression of RIP140 reduced glioma cell proliferation and migration, induced cellular apoptosis, and sensitized GBM cells to TMZ. Conversely, knockdown of RIP140 increased TMZ resistance. Taken together, our results suggest that RIP140 prolongs the survival of patients with GBM both by inhibiting tumor cell proliferation and migration and by increasing cellular sensitivity to chemotherapy. This study helps improve our understanding of glioma recurrence and may facilitate the development of more effective treatments.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE