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. 2021 May 1;22(9):4819. doi: 10.3390/ijms22094819

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Several microRNAs (miRNAs) downregulated simultaneously in the three types of tumor microenvironment (TME) cells are hallmarks of eukaryotic aging. (A) Heatmap of all geromiRs and their annotation with different aging hallmarks. D: altered DNA damage response, T: loss of telomeres, G: changes in gene regulation, M: DNA methylation, H: histone modifications, S: regulation of splicing, P: changes to protein homeostasis, N: altered nutrient sensing, m: mitochondrial dysfunction, S: cellular senescence, E: stem cell exhaustion, I: inflammaging, s: Sirtuins, h: stem cell homeostasis, i: insulin/IGF1, C: altered intercellular communication. The samples are denoted with E, I and K for endothelial, Ito and Kupffer cells, and C and T for the control and the TME cells, respectively. TP and TM denote colorectal cancer (CRC) primary and liver metastasis cells, respectively. (B) Violin plots of the expression distribution of the miRNAs associated with the hallmarks of eukaryotic aging. The crosses represent the position of the means, while the black points represent the spread of the expression of the miRNAs used to build the distributions.