MicroRNA-Mediated Downregulation of HMGB2 Contributes to Cellular Senescence in Microvascular Endothelial Cells

High mobility group box 2 (HMGB2) is a non-histone chromosomal protein involved in various biological processes, including cellular senescence. However, its role in cellular senescence has not been evaluated extensively. To determine the regulatory role and mechanism of HMGB2 in cellular senescence,...

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Published in:Cells (Basel, Switzerland) Switzerland), 2022-02, Vol.11 (3), p.584
Main Authors: Jo, Hye-Ram, Jeong, Jae-Hoon
Format: Article
Language:English
Subjects:
Aging
Cell cycle
Cell proliferation
Cellular Senescence - genetics
DNA damage
Down-Regulation - genetics
Endothelial cells
Endothelial Cells - metabolism
Gene expression
high mobility group box 2
High mobility group proteins
Histones
HMGB2 Protein - genetics
HMGB2 Protein - metabolism
Laboratories
microRNA
MicroRNAs
MicroRNAs - metabolism
microvascular endothelial cell
Microvasculature
miRNA
Polymerase chain reaction
Potassium
Proteins
Radiation
Senescence
siRNA
Transcription
Transcription Factors - metabolism
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Summary:High mobility group box 2 (HMGB2) is a non-histone chromosomal protein involved in various biological processes, including cellular senescence. However, its role in cellular senescence has not been evaluated extensively. To determine the regulatory role and mechanism of HMGB2 in cellular senescence, we performed gene expression analysis, senescence staining, and tube formation assays using young and senescent microvascular endothelial cells (MVECs) after small RNA treatment or overexpression. expression decreased with age and was regulated at the transcriptional level. siRNA-mediated downregulation inhibited cell proliferation and accelerated cellular senescence. In contrast, ectopic overexpression delayed senescence and maintained relatively higher tube-forming activity. To determine the downregulation mechanism, we screened miRNAs that were significantly upregulated in senescent MVECs and selected HMGB2-targeting miRNAs. Six miRNAs, miR-23a-3p, 23b-3p, -181a-5p, -181b-5p, -221-3p, and -222-3p, were overexpressed in senescent MVECs. Ectopic introduction of miR-23a-3p, -23b-3p, -181a-5p, -181b-5p, and -221-3p, with the exception of miR-222-3p, led to the downregulation of , upregulation of senescence-associated markers, and decreased tube formation activity. Inhibition of miR-23a-3p, -181a-5p, -181b-5p, and -221-3p delayed cellular senescence. Restoration of expression using miRNA inhibitors represents a potential strategy to overcome the detrimental effects of cellular senescence in endothelial cells.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells11030584