Glioma, as one of the most aggressive tumors, is hardly cleaned by surgical removal, leading to a low survival rate. m6A is an internal modification in RNA and plays an important role in many kinds of cancers. In our study, we detected that the m6A level was decreased in glioma tissue, which might be caused by decreased METTL3 and increased FTO levels. We upregulated the m6A level in U251 cells by overexpressing METTL3. The results showed that a high level of m6A led to a reduced migration and proliferation ability, and vice versa. Finally, we performed a TUNEL assay and showed that m6A regulated cell proliferation by influencing apoptosis of U251 cells through regulating HSP90 expression.

Keywords:
Apoptosis, Glioma, m6A, Proliferation
1.
Afshordel S, Kern B, Clasohm J, König H, Priester M, et al: Lovastatin and perillyl alcohol inhibit glioma cell invasion, migration, and proliferation-impact of Ras-/Rho-prenylation. Pharmacol Res 91:69-77 (2015).
2.
An L, Liu Y, Wu A, Guan Y: microRNA-124 inhibits migration and invasion by down-regulating ROCK1 in glioma. PLoS One 8:e69478 (2013).
3.
Batchelor TT, Reardon DA, Groote FJ, Wick W, Weller M: Antiangiogenic therapy for glioblastoma: current status and future prospects. Clin Cancer Res 20:5612-5619 (2014).
4.
Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, et al: Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485:201-206 (2012).
5.
Garcia-Gomez A, Li T, Kerick M, Català-Moll F, Comet NR, et al: TET2- and TDG-mediated changes are required for the acquisition of distinct histone modifications in divergent terminal differentiation of myeloid cells. Nucleic Acids Res 45:10002-10017 (2017).
6.
Geula S, Moshitch-Moshkovitz S, Dominissini D, Mansour AA, Kol N, et al: Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 347:1002-1006 (2015).
7.
Haussmann IU, Bodi Z, Sanchez-Moran E, Mongan NP, Archer N, et al: m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature 540:301-304 (2016).
8.
Hongay CF, Orr-Weaver TL: Drosophila Inducer of MEiosis 4 (IME4) is required for Notch signaling during oogenesis. Proc Natl Acad Sci USA 108:14855-14860 (2011).
9.
Jaffrey SR, Kharas MG: Emerging links between m6A and misregulated mRNA methylation in cancer. Genome Med 9:2 (2017).
10.
Lence T, Akhtar J, Bayer M, Schmid K, Spindler L, et al: m6A modulates neuronal functions and sex determination in Drosophila. Nature 540:242-247 (2016).
11.
Li Z, Weng H, Su R, Weng X, Zuo Z, et al: FTO plays an oncogenic role in acute myeloid leukemia as a N6-Methyladenosine RNA demethylase. Cancer Cell 31:127-141 (2017).
12.
Ma EG, Bai YF, Cao W, Cao Y, Huang YG, et al: Cytosine 5-hydroxymethylation regulates VHL gene expression in renal clear cell carcinoma. Oncotarget 8:63780-63787 (2017).
13.
Ma Q, Lu H, Xu Z, Zhou Y, Ci W: Mouse olfactory bulb methylome and hydroxymethylome maps reveal noncanonical active turnover of DNA methylation. Epigenetics 12:708-714 (2017).
14.
Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR: Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149:1635-1646 (2012).
15.
Zhang C, Samanta D, Lu H, Bullen JW, Zhang H, et al: Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proc Natl Acad Sci USA 113:E2047-256 (2016).
© 2019 S. Karger AG, Basel
2019
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.