Histone deacetylase regulates high mobility group A2-targeting microRNAs in human cord blood-derived multipotent stem cell aging.
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.
Lee
Seunghee
S
Adult Stem Cell Research Center, Seoul National University, Republic of Korea.
Jung
Ji-Won
JW
Park
Sang-Bum
SB
Roh
Kyounghwan
K
Lee
Su Yeon
SY
Kim
Ju Han
JH
Kang
Soo-Kyung
SK
Kang
Kyung-Sun
KS
D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D057890:Epigenomics; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D046228:Microarray Analysis; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014635:Valproic Acid / Q000494:pharmacology
D025743:HMGA2 Protein; D006609:High Mobility Group Proteins; D056572:Histone Deacetylase Inhibitors; D035683:MicroRNAs; D014635:Valproic Acid; D006655:Histone Deacetylases