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. 2022 Mar 30;7:87. doi: 10.1038/s41392-022-00902-6

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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. 4 — Oxaliplatin resistance following MEIS1 suppression is critically dependent on enhanced FEN1 expression. a GSEA plots showing that MEIS1 mRNA expression negatively correlated with DNA damage repair signatures in the TCGA datasets. b GSVA enrichment analysis showing the DNA repair and apoptosis pathways in the high- or low-MEIS1 groups. c Significant correlations were observed between MEIS1 expression and DNA damage repair pathway genes in the GSE9348, TCGA, GSE21510, and GSE32323 datasets. These genes were detected with | R | > 0.3 as the cutoff criterion in the four-cohort profile. Red represents positive correlations and blue represents negative correlations, Genes that were exclusively positive or negative correlations in all four datasets were screened as candidate genes. d qPCR results of the indicated RNA levels in cells transfected with oe-NC or oe MEIS1. e Luciferase reporter assay of the effect of FEN1, SNAPC4, and ZWINT on the transcriptional activity of the MEIS1 promoter. f Schematic showing putative MEIS1-binding sites on the promoter region of FEN1 and design of the indicated primers (top). ChIP-qPCR analysis of the enrichment of MEIS1 on the FEN1 promoter relative to that in control IgG-treated Caco2 and SW480 cells (bottom). g, h Representative western blot image of the FEN1 protein levels in cells with MEIS1 knockdown (g) or overexpression (h). i, j IHC of MEIS1 and FEN1 expression in CRC. Data are presented as a representative image (i) (top, ×20 magnification; bottom, ×40 magnification) and summary graphs(j). Scale bar, 100 µm. k Western blot analyses of MEIS1 and FEN1 expression in Caco2 and SW480 cells. l–n The proliferation of Caco-2 and SW480 cells was evaluated by the CCK-8 (l), cell colony formation (m), and EdU assays (n). o The cell viability and the IC50 values of SW480 cells was evaluated by the CCK-8 following increasing concentrations of oxaliplatin treatment for 48 h. The data are presented as the mean ± SEM from three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001