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. 2022 Mar 19;20:34. doi: 10.1186/s12964-022-00834-2

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© The Author(s) 2022

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. 3 — Combination of WNT974 and ART induces KRAS protein degradation by increasing anaphase promoting complex subunit 2 (ANAPC2) expression. A HCT116 cells were treated with 20 μM WNT974, 20 μM ART or the combination of both for 48 h. Heat map showing the PCR array results. B The numbers of up- or down-regulated genes in the PCR array. C The mRNA expressions of CUL7 (cullin), ANAPC2 (anaphase promoting complex subunit 2), UBE2M (ubiquitin conjugating enzyme E2M), SYVN1 (synoviolin 1) and RNF123 (RING finger protein123) in the CRC cells after the treatments. KRAS expression in the CRC cells after siRNA-mediated knockdown of D CUL7, E ANAPC2, F UBE2M, G RNF123, H SYVN1, upper panel showing the expressions of CUL7, ANAPC2, UBE2M, RNF123 and SYNV1 in these cells. I Protein expressions of ANAPC2 in ANAPC2-overexpressed CRC cells. J Protein expressions of KRAS in ANAPC2-overexpressed CRC cells in the presence or absence of MG132. K CRC cells were treated with 20 μM WNT974, 20 μM ART or the combination of both for 48 h. The protein expression of ANAPC2 after the treatments. Shown is mean ± SE, n = 3 individual experiments, *p < 0.05, *** < 0.001 compared to control; a < 0.05, compared to ART; b < 0.05, compared to WNT974