Molecular mechanism of m(6)A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells

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...

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Autores principales: Wu, Quansheng, Yin, Xiaofeng, Zhao, Wenbo, Xu, Wenli, Chen, Laizhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043209/
https://www.ncbi.nlm.nih.gov/pubmed/35474040
http://dx.doi.org/10.1038/s41420-022-00979-6
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author Wu, Quansheng
Yin, Xiaofeng
Zhao, Wenbo
Xu, Wenli
Chen, Laizhao
author_facet Wu, Quansheng
Yin, Xiaofeng
Zhao, Wenbo
Xu, Wenli
Chen, Laizhao
author_sort Wu, Quansheng
collection PubMed
description 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. N(6) methyladenosine (m(6)A) 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 m(6)A 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 m(6)A modification upregulated circDLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma.
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spelling pubmed-90432092022-04-28 Molecular mechanism of m(6)A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells Wu, Quansheng Yin, Xiaofeng Zhao, Wenbo Xu, Wenli Chen, Laizhao Cell Death Discov Article 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. N(6) methyladenosine (m(6)A) 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 m(6)A 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 m(6)A modification upregulated circDLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma. Nature Publishing Group UK 2022-04-26 /pmc/articles/PMC9043209/ /pubmed/35474040 http://dx.doi.org/10.1038/s41420-022-00979-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wu, Quansheng
Yin, Xiaofeng
Zhao, Wenbo
Xu, Wenli
Chen, Laizhao
Molecular mechanism of m(6)A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells
title Molecular mechanism of m(6)A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells
title_full Molecular mechanism of m(6)A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells
title_fullStr Molecular mechanism of m(6)A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells
title_full_unstemmed Molecular mechanism of m(6)A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells
title_short Molecular mechanism of m(6)A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells
title_sort molecular mechanism of m(6)a methylation of circdlc1 mediated by rna methyltransferase mettl3 in the malignant proliferation of glioma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043209/
https://www.ncbi.nlm.nih.gov/pubmed/35474040
http://dx.doi.org/10.1038/s41420-022-00979-6
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