Molecular mechanism of m6A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells

Abstract

Glioma is an intracranial malignant tumor and remains largely incurable. Circular RNAs are prominent modulators in glioma progression. This study investigated the function of circular RNA DLC1 (circDLC1) in the malignant proliferation of glioma cells. circDLC1 expression in glioma tissues and cells was determined using RT-qPCR. The effect of circDLC1 on the malignant proliferation of glioma cells was analyzed using CCK-8, colony formation, and EdU staining assays. METTL3, miR-671-5p, and CTNNBIP1 expressions were determined. N6 methyladenosine (m6A) level of circDLC1 was analyzed using MeRIP. The binding relationship between miR-671-5p and circDLC1 or CTNNBIP1 was verified using RNA pull-down and dual-luciferase assays. A xenograft tumor model was established in nude mice to verify the effect of METTL3-mediated circDLC1 on glioma in vivo. circDLC1 was poorly expressed in glioma. circDLC1 overexpression suppressed glioma cell proliferation. Mechanically, METTL3-mediated m6A modification enhanced circDLC1 stability and upregulated circDLC1 expression in glioma. circDLC1 upregulated CTNNBIP1 transcription by competitively binding to miR-671-5p. METTL3 overexpression repressed the malignant proliferation of glioma via circDLC1/miR-671-5p/CTNNBIP1 in vivo. Collectively, METTL3-mediated m6A modification upregulated circDLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma.

Latest updates on cellular and molecular biomarkers of gliomas

“…Other circRNAs may also prevent the proliferation of glioma cells and have a protective value. An example is circDCL1, whereby upregulation of this circRNA through METTL3-mediated m6A modification repressed the malignant proliferation of glioma cells ( 133 ). Recent studies also suggest that cicRNAs can affect multiple pathways of gliomagenesis, including the tumor microenvironment.…”

Identification of N6-Methyladenosine-Related Gene Based Prognostic Signature to Predict Survival and Potential Therapeutic Drugs in Glioma

“…Accumulating evidence has revealed the unique role of m6A RNA methylation in the genesis and development of cancer including glioma. A series of studies using the knockdown model of METTL3 and METTL14 observed a reduction of m6A extent accompanied by upregulation of oncogenes and downregulation of tumor suppressors [20,21] . On the contrary, overexpression of METTL3 leads to decreased proliferation and migration of glioma cells.…”

m6A-modified circRNAs: detections, mechanisms, and prospects in cancers

“…Recent research into the molecular mechanism of glioma malignant proliferation has sparked widespread concern. By using m 6 A level detection and MeRIP assays, Wu et al discovered that METTL3-mediated m 6 A modification can enhance the stability and expression of circDLC1, thereby promoting the competitive binding of circDLC1 and miR-671-5p, facilitating Catenin Beta Interacting Protein 1 (CTNNBIP1) transcription, and ultimately suppressing the malignant proliferation of glioma cells (Wu et al 2022).…”