M6A-methylated CircPOLR2B Forms an R-loop and Regulates the Biological Behavior of Glioma Stem Cells Through Positive Feedback Loops

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2024 Aug 1

PMID 39090090

Authors

Hongda Lin

Zheng Cui

Tiange E

Hailing Xu

Di Wang

Ping Wang

Xuelei Ruan

Libo Liu

Yixue Xue

Affiliations

Soon will be listed here.

Abstract

Glioma is the most common primary brain tumor, and targeting glioma stem cells (GSCs) has become a key aspect of glioma treatment. In this study, we discovered a molecular network in which circRNA forms an R-loop structure with its parental gene to regulate the biological behavior of GSCs. Genes with abnormal expression in GSCs were screened using RNA-seq and circRNA microarray analyses. The study results showed that high expression of YTHDC1 in GSCs promoted the transportation of N6-methyladenosine (m6A)-modified circPOLR2B from the nucleus to the cytoplasm. Decreased circPOLR2B levels in the nucleus resulted in fewer R-loop structures formed with its parental gene POLR2B. This reduction in R-loop structures relieved the inhibitory effect on POLR2B transcription and upregulated PBX1 expression through alternative polyadenylation (APA) action, thereby promoting the malignant biological behavior of GSCs. Knockdown of YTHDC1, POLR2B, and PBX1 reduced xenograft tumor volume and prolonged the survival of nude mice. The YTHDC1/circPOLR2B/POLR2B/PBX1 axis plays a regulatory role in the biological behavior of GSCs, offering potential targets and novel strategies for the treatment of glioma.

Citing Articles

Cross-regulation of RNA methylation modifications and R-loops: from molecular mechanisms to clinical implications.

Wu Y, Lin S, Chen H, Zheng X Cell Mol Life Sci. 2024; 82(1):1.

PMID: 39656315 PMC: 11631829. DOI: 10.1007/s00018-024-05536-1.

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