Related Experiment Video

Updated: Jun 18, 2025

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells
10:28

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

Published on: January 10, 2018

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M6A-methylated circPOLR2B forms an R-loop and regulates the biological behavior of glioma stem cells through positive

Hongda Lin1,2,3, Zheng Cui1,2,3, Tiange E1,2,3

  • 1Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.

Cell Death & Disease
|August 1, 2024
PubMed

Insights

This study reveals a novel molecular network involving circRNA and R-loop structures that regulate glioma stem cells. Targeting the YTHDC1/circPOLR2B/POLR2B/PBX1 axis offers new therapeutic strategies for glioma.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Glioma, a common brain tumor, necessitates targeting glioma stem cells (GSCs) for effective treatment.
  • Understanding the molecular mechanisms governing GSC behavior is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To elucidate a novel molecular network involving circular RNA (circRNA) and R-loop structures in regulating GSC malignant behaviors.
  • To identify potential therapeutic targets within this network for glioma treatment.

Main Methods:

  • RNA sequencing (RNA-seq) and circRNA microarray analyses were employed to screen for aberrantly expressed genes in GSCs.
  • Functional studies involved knockdown experiments of key molecular players (YTHDC1, circPOLR2B, POLR2B, PBX1) in vitro and in vivo xenograft models.

Main Results:

  • High YTHDC1 expression promotes the nuclear export of m6A-modified circPOLR2B, reducing nuclear R-loop formation with POLR2B.
  • Reduced R-loops relieve POLR2B transcriptional inhibition, leading to PBX1 upregulation via alternative polyadenylation (APA), thus promoting GSC malignancy.
  • Knockdown of YTHDC1, circPOLR2B, POLR2B, or PBX1 significantly reduced tumor volume and improved survival in mice.

Conclusions:

  • The YTHDC1/circPOLR2B/POLR2B/PBX1 axis is identified as a key regulatory pathway in GSC biological behavior.
  • This axis represents a promising therapeutic target and offers novel treatment strategies for glioma.

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