miR-543 and miR-590-3p regulate human mesenchymal stem cell aging via direct targeting of AIMP3/p18
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Previously, AIMP3 (aminoacyl-tRNAsynthetase-interacting multifunctional protein-3) was shown to be involved in the macromolecular tRNA synthetase complex or to act as a tumor suppressor. In this study, we report a novel role of AIMP3/p18 in the cellular aging of human mesenchymal stem cells (hMSCs). We found that AIMP3/p18 expression significantly increased in senescent hMSCs and in aged mouse bone marrow-derived MSCs (mBM-MSCs). AIMP3/p18 overexpression is sufficient to induce the cellular senescence phenotypes with compromised clonogenicity and adipogenic differentiation potential. To identify the upstream regulators of AIMP3/p18 during senescence, we screened for potential epigenetic regulators and for miRNAs. We found that the levels of miR-543 and miR-590-3p significantly decreased under senescence-inducing conditions, whereas the AIMP3/p18 protein levels increased. We demonstrate for the first time that miR-543 and miR-590-3p are able to decrease AIMP3/p18 expression levels through direct binding to the AIMP/p18 transcripts, which further compromised the induction of the senescence phenotype. Taken together, our data demonstrate that AIMP3/p18 regulates cellular aging in hMSCs possibly through miR-543 and miR-590-3p.
KeywordsAIMP3/p18 Stem cell Aging miR-543 miR-590-3p
aminoacyl-tRNAsynthetase-interacting multifunctional protein-3
mesenchymal stem cells
human umbilical cord blood
mouse bone marrow
acetyl histone H4
histone H3 lysine 4 trimethylation
histone H3 lysine 27 trimethylation
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: A120176) and by the Research Institute for Veterinary Science, Seoul National University.
Conflict of interest
The authors declare no conflicts of interest.
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