RRC ID 73284
Author Hattori EY, Masuda T, Mineharu Y, Mikami M, Terada Y, Matsui Y, Kubota H, Matsuo H, Hirata M, Kataoka TR, Nakahata T, Ikeda S, Miyamoto S, Sugiyama H, Arakawa Y, Kamikubo Y.
Title A RUNX-targeted gene switch-off approach modulates the BIRC5/PIF1-p21 pathway and reduces glioblastoma growth in mice.
Journal Commun Biol
Abstract Glioblastoma is the most common adult brain tumour, representing a high degree of malignancy. Transcription factors such as RUNX1 are believed to be involved in the malignancy of glioblastoma. RUNX1 functions as an oncogene or tumour suppressor gene with diverse target genes. Details of the effects of RUNX1 on the acquisition of malignancy in glioblastoma remain unclear. Here, we show that RUNX1 downregulates p21 by enhancing expressions of BIRC5 and PIF1, conferring anti-apoptotic properties on glioblastoma. A gene switch-off therapy using alkylating agent-conjugated pyrrole-imidazole polyamides, designed to fit the RUNX1 DNA groove, decreased expression levels of BIRC5 and PIF1 and induced apoptosis and cell cycle arrest via p21. The RUNX1-BIRC5/PIF1-p21 pathway appears to reflect refractory characteristics of glioblastoma and thus holds promise as a therapeutic target. RUNX gene switch-off therapy may represent a novel treatment for glioblastoma.
Volume 5(1)
Pages 939
Published 2022-9-9
DOI 10.1038/s42003-022-03917-5
PII 10.1038/s42003-022-03917-5
PMID 36085167
PMC PMC9463152
MeSH Animals Apoptosis / genetics Brain Neoplasms* / genetics Core Binding Factor Alpha 2 Subunit DNA Helicases Glioblastoma* / genetics Mice Oncogenes
IF 4.165
DNA material pENTR4-H1tetOx1 (RDB07916) CS-RfA-ETV (RDB08020) CS-RfA-ETBsd (RDB07917)