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. 2022 Jul 18;45(4):621–638. doi: 10.1007/s13402-022-00688-3

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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/.

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Fig. 6 — The impact of 15 mCRC-EV-miRs on MET in the metastasized cells. (A) 165 mRNA gene targets potentially under regulation by the 15 mCRC-EV-miRs were mapped based on prior experimental evidence (microRNA Target Filter analysis module of IPA), functional enrichment of which were further uncovered by the Core Analysis of IPA (top 20 canonical pathways are shown). The colors of the bars correspond to the possibility of whether the activity of the enriched pathway could be predicted (white, yes; gray, no). (B-G) Cohort-wide correlation of miRNA expression with EMT scores. Expression levels of the indicated miRs, respectively miR-200c-3p (B), miR-200b-5p (C), miR-194-5p (D), miR-552-3p (E), miR-320b (F), miR-141-3p (G), in each patient were analyzed for the extent of correlation with the respective EMT score, as shown in the dot plots. Correlation coefficient and statistical significance of each comparison are also denoted. (H) Schematic depiction of the potential involvement of progression-dependent circulating EV-miRs in reprogramming the metastasized cells into a metastasis-favorable MET state