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Updated: Jun 15, 2026

Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
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A RUNX-targeted gene switch-off approach modulates the BIRC5/PIF1-p21 pathway and reduces glioblastoma growth in mice

Etsuko Yamamoto Hattori1,2, Tatsuya Masuda2, Yohei Mineharu1

  • 1Department of Neurosurgery, Graduate School of Medicine, Kyoto University; Kyoto City, Kyoto, 606-8507, Japan.

Communications Biology
|September 9, 2022
PubMed

Insights

RUNX1 promotes glioblastoma malignancy by suppressing p21 and enhancing anti-apoptotic genes. A novel gene switch-off therapy targeting RUNX1 shows promise for treating this aggressive brain tumor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Glioblastoma is a highly malignant adult brain tumor.
  • Transcription factors, including RUNX1, play roles in glioblastoma malignancy, but their precise functions are not fully understood.

Purpose of the Study:

  • To elucidate the role of RUNX1 in glioblastoma malignancy.
  • To investigate the potential of a RUNX1-targeted gene switch-off therapy for glioblastoma treatment.

Main Methods:

  • Investigated the effect of RUNX1 on p21, BIRC5, and PIF1 expression in glioblastoma.
  • Developed and tested alkylating agent-conjugated pyrrole-imidazole polyamides for gene switch-off therapy targeting RUNX1 DNA binding sites.

Main Results:

  • RUNX1 was found to downregulate p21 by enhancing BIRC5 and PIF1 expression, contributing to glioblastoma's anti-apoptotic properties.
  • The gene switch-off therapy successfully decreased BIRC5 and PIF1 expression, induced apoptosis, and caused cell cycle arrest via p21.
  • The RUNX1-BIRC5/PIF1-p21 pathway was identified as a key mechanism underlying glioblastoma's refractoriness.

Conclusions:

  • RUNX1 promotes glioblastoma malignancy and resistance through the BIRC5/PIF1-p21 pathway.
  • RUNX gene switch-off therapy targeting RUNX1 offers a potential novel therapeutic strategy for glioblastoma.

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