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. 2022 Jan 29;41(11):1622–1633. doi: 10.1038/s41388-022-02185-1

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© The Author(s) 2022

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/.

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Fig. 5 — A Heatmap showing the expression changes of METTL3-KD and Control HuCC-T1 cell. B The m⁶A consensus sequence motifs in HuCC-T1 and HCCC-9810 cells was identified. C Scatter plot shows the genes with m⁶A modification (fold enrichment >4 and P < 0.05) in both HuCC-T1 and HCCC-9810 cells and differentially expressed (Log₂foldchange > 0.5 and P < 0.05) in HuCC-T1 cells after METTL3 silencing. D Relative expression of IFIT2 in METTL3-KD and Control HuCC-T1 cells. E RT-qPCR analysis of IFIT2 after METTL3 silencing in HCCC-9810 cells. F Integrative genomics viewer (IGV) plots indicates m⁶A peaks at IFIT2 mRNAs in MeRIP-seq of ICC cells. The y axis shows the sequence read number, and the blue boxes represent protein-coding exons. G RT-qPCR analysis of IFIT2 mRNA expression in HuCC-T1 xenograft models after METTL3 knockdown or not. H Bar graphs indicate the correlation of METTL3 expression with IFIT2 expression in ICC specimens. I Kaplan–Meier survival curves of DFS in 96 patients with ICC. (IFIT2 low expression, n = 62 vs. IFIT2 high expression, n = 34). The P value was calculated using the log-rank test. HR hazard ratio. J Kaplan–Meier survival curves of OS in 96 patients with ICC. (IFIT2 low expression, n = 62 vs. IFIT2 high expression, n = 34). The P value was calculated using the log-rank test. HR hazard ratio. The results are presented as mean ± SD of three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001, according to Student’s t test.