title: miR-543 and miR-590-3p regulate human mesenchymal stem cell aging via direct targeting of AIMP3/p18.
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.
authors.affiliation: Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, Republic of Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Lee
authors.forename: Kyung-Rok
authors.initials: KR
authors.lastname: Yu
authors.forename: Young-Sil
authors.initials: YS
authors.lastname: Ryu
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Oh
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Hong
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Kwang-Won
authors.initials: KW
authors.lastname: Seo
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D016685:Mitomycin / Q000494:pharmacology; D010445:Peptide Elongation Factors / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C529799:EEF1E1 protein, human; C577592:MIRN543 microRNA, human; D035683:MicroRNAs; D010445:Peptide Elongation Factors; D025521:Tumor Suppressor Proteins; D016685:Mitomycin