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. 2021 Feb 19;12(2):201. doi: 10.1038/s41419-021-03489-y

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© The Author(s) 2021

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. 6 — a–c Pearson correlation analysis of the relationship between CDKN2B-AS1, IGF2BP3, and NUF2 levels in TCGA-KIRC dataset (a) and 42 paired KIRC tissues and adjacent normal tissues (b), normal tissues are shown as blue circles and tumor tissues as red circles; the correlation coefficient between each two markers is shown in c. d, e Kaplan–Meier analysis of overall survival and disease-free survival for KIRC patients in TCGA dataset based on the number of upregulated molecular markers; CDKN2B-AS1, NUF2, and IGF2BP3 expression was stratified by the individual medians by RNA-seq data, and the patients were divided into four groups as indicated. f, g ROC curve analysis of overall survival (f) and disease-free survival (g) for CDKN2B-AS1, NUF2, and IGF2BP3 as individual biomarkers or as a combined panel (containing CDKN2B-AS1, NUF2, and IGF2BP3). h–k ROC curve analysis for CDKN2B-AS1, NUF2, and IGF2BP3 as individual biomarkers or as a combined panel to discriminate KIRC patients with high tumor grades (G3 and G4) from those with low tumor grades (G1 and G2) (h); KIRC patients with stages III and IV from those with stages I and II (i); KIRC patients with distant metastasis from patients without distant metastasis (j), and KIRC patients with lymph node metastasis from patients without lymph node metastasis (k). **p < 0.01, *p < 0.05. l Schematic diagram of the IGF2BP3/CDKN2B-AS1/NUF2 axis regulating tumor growth and metastasis in KIRC cells. CDKN2B-AS1 is stabilized by specifically binding to IGF2BP3 and acts as a modular scaffold of the CBP and SMYD3 epigenetic-modifying complex to increase H3K27ac and H3K4me3 modification in the promoter region of NUF2, thereby enhancing NUF2 transcription, and promoting tumor cell growth and metastasis.