Histone deacetylase regulates high mobility group A2-targeting microRNAs in human cord blood-derived multipotent stem cell aging.

Cellular and Molecular Life Sciences : CMLS
Seunghee LeeKyung-Sun Kang

Abstract

Cellular senescence involves a reduction in adult stem cell self-renewal, and epigenetic regulation of gene expression is one of the main underlying mechanisms. Here, we observed that the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) caused by inhibition of histone deacetylase (HDAC) activity leads to down-regulation of high mobility group A2 (HMGA2) and, on the contrary, to up-regulation of p16(INK)⁴(A), p21(CIP)¹(/WAF)¹ and p27(KIP)¹. We found that let-7a1, let-7d, let-7f1, miR-23a, miR-26a and miR-30a were increased during replicative and HDAC inhibitor-mediated senescence of hUCB-MSCs by microRNA microarray and real-time quantitative PCR. Furthermore, the configurations of chromatins beading on these miRNAs were prone to transcriptional activation during HDAC inhibitor-mediated senescence. We confirmed that miR-23a, miR-26a and miR-30a inhibit HMGA2 to accelerate the progress of senescence. These findings suggest that HDACs may play important roles in cellular senescence by regulating the expression of miRNAs that target HMGA2 through histone modification.

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Methods Mentioned

BETA
acetylation
PCR
electrophoresis
transfection
transfections
immunoprecipitation
ChIP
histone acetylation

Software Mentioned

Prism 7000 sequence detection system
Pictar
Targetscan
Miranda
Image J
ImageJ
GeneSpring GX

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