A RUNX-targeted gene switch-off approach modulates the BIRC5/PIF1-p21 pathway and reduces glioblastoma growth in mice

Interfering with RUNX family proteins reduces glioblastoma growth in mice and reveals pathways involved in the maintenance of tumour growth. 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.

Automated summary

Interfering with RUNX family proteins can reduce the growth of glioblastoma in mice and identify pathways involved in tumor growth maintenance. Specifically, the study reveals that RUNX1, a transcription factor, downregulates p21 by enhancing the expressions of BIRC5 and PIF1, thus conferring anti-apoptotic properties on glioblastoma. Gene switch-off therapy targeting RUNX1 shows promising results by decreasing the expression levels of BIRC5 and PIF1, inducing apoptosis and cell cycle arrest. This pathway may serve as a therapeutic target for glioblastoma.