miR-543 and miR-590-3p regulate human mesenchymal stem cell aging via direct targeting of AIMP3/p18

Seunghee Lee, Kyung Rok Yu, Young Sil Ryu, Young Sun Oh, In Sun Hong, Hyung Sik Kim, Jin Young Lee, Sunghoon Kim, Kwang Won Seo, Kyung Sun Kang

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Abstract

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.

Original languageEnglish
Article number9724
JournalAge
Volume36
Issue number6
DOIs
Publication statusPublished - 2014 Nov 21

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All Science Journal Classification (ASJC) codes

  • Ageing
  • Geriatrics and Gerontology

Cite this

Lee, S., Yu, K. R., Ryu, Y. S., Oh, Y. S., Hong, I. S., Kim, H. S., Lee, J. Y., Kim, S., Seo, K. W., & Kang, K. S. (2014). miR-543 and miR-590-3p regulate human mesenchymal stem cell aging via direct targeting of AIMP3/p18. Age, 36(6), [9724]. https://doi.org/10.1007/s11357-014-9724-2