Molecular mechanism of m6A methylation of circDCL1 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 (circDCL1) in the malignant proliferation of glioma cells. circDCL1 expression in glioma tissues and cells was determined using RT-qPCR. The effect of circDCL1 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 circDCL1 was analyzed using MeRIP. The binding relationship between miR-671-5p and circDCL1 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 circDCL1 on glioma in vivo. circDCL1 was poorly expressed in glioma. circDCL1 overexpression suppressed glioma cell proliferation, while circDCL1 silencing showed an opposite trend. Mechanically, METTL3-mediated m6A modification enhanced circDCL1 stability and upregulated circDCL1 expression in glioma. circDCL1 upregulated CTNNBIP1 transcription by competitively binding to miR-671-5p. METTL3 overexpression repressed the malignant proliferation of glioma via circDCL1/miR-671-5p/CTNNBIP1 in vivo. Collectively, METTL3-mediated m6A modification upregulated circDCL1 expression, and circDCL1 promoted CTNNBIP1 transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma.