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. 2020 Apr 3;19:72. doi: 10.1186/s12943-020-01190-w

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© The Author(s) 2020

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — METTL3 is closely correlated with glycolytic metabolism in CRC. (a) The correlation matrix showed the relationship between the expression of m⁶A genes and SUV_max (FDG maximal standardized uptake value) in 47 CRC patients of Cohort 1. (b) Correlation between FDG uptake (SUV_max) and METTL3 expression in 47 CRC patients of Cohort 1. (c) Correlation between FDG uptake (SUV_max) and METTL3 expression in 30 CRC patients of another independent cohort (GSE110225). (d) Representative PET/CT images and METTL3 immunohistochemical images of CRC patients with FDG high uptake and FDG low uptake in Cohort 1. (e) Statistical analysis of METTL3 expression in CRC patients with FDG high uptake and patients with FDG low uptake, nonparametric Mann-Whitney test. (f) LC-MS/MS quantification of the m⁶A/A ratio in poly(A) RNA isolated from CRC patients with FDG high uptake or FDG low uptake in Cohort 1, nonparametric Mann-Whitney test. (g) Representative images and relative quantitative information of m⁶A dot blot assay showed global m⁶A abundance in CRC patients with FDG high uptake or FDG low uptake in Cohort 1. MB, methylene blue staining (as a loading control). (h) ssGSEA analysis was performed to show the pathways closely correlated with METTL3 expression levels in CRC cells; n = 3. (i) LC-MS/MS-based analysis showed the major metabolites altered in the glycolytic pathway in HCT116 METTL3-KO cells relative to WT cells. The differentially expressed metabolites (p < 0.05) were highlighted in red; n = 3. (WT, wild type; METTL3-KO, METTL3-knockout)