期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 146, 期 -, 页码 1-11出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2015.03.001
关键词
Human dental pulp cell; Senescence; MicroRNAs; GRB2; RAS-MAPK signaling pathways
资金
- Sichuan Province Science and technology support program [2014SZ0019]
- Zhejiang Province Natural Science Foundation of China [LQ14H140001]
As a kind of endogenous noncoding small RNA, MicroRNA (miRNA) plays important roles of regulation to various physiological functions, while its affections on senescence of human dental pulp cell (HDPCs) are still unknown. Thus, we identified the senescence-associated miRNAs in HDPCs by microarray analysis, predicted their targets and regulatory signaling pathway by gene ontology and Kyoto encyclopedia of genes and genomes pathway database analysis. After validated, the senescence-associated miRNAs' expression level was up- and down-regulated using lentivirus package and cell transfection to find its role in HDPCs' morphology, proliferation, apoptosis, and mineralization. The results showed 27 miRNAs differentially expressed at least 1.5-fold, of which 16 were up-regulated and 11 down-regulated, the function of their targets was mainly focused on signal transduction, cell proliferation, apoptosis, and transcription regulation. According to the change fold, we speculated that miR-433 could be one of the vital senescence-associated miRNAs of HDPCs and found its target (GRB2), validated that miR-433 could negatively regulate GRB2 and the RAS-MAPK signaling pathway, leading to the decline of proliferation and mineralization ability of HDPCs and the acceleration of cell apoptosis, suggesting the regulation of miR-433 might be the potential target to promote repair and regeneration of HDPCs in the elderly. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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