scholarly journals miR-377 induces senescence in human skin fibroblasts by targeting DNA methyltransferase 1

2017 ◽  
Vol 8 (3) ◽  
pp. e2663-e2663 ◽  
Author(s):  
Hong-fu Xie ◽  
Ying-zi Liu ◽  
Rui Du ◽  
Ben Wang ◽  
Meng-ting Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Skin ◽  
Dna Methyltransferase ◽  
Skin Aging ◽  
Skin Fibroblasts ◽  
Luciferase Reporter ◽  
Dna Methyltransferase 1 ◽  
Human Skin Fibroblasts ◽  
Dnmt1 Expression ◽  
Methyltransferase 1

Abstract Skin aging is a complicated physiological process and epigenetic feature, including microRNA-mediated regulation and DNA methylation, have been shown to contribute to this process. DNA methylation is regulated by DNA methyltransferase, of which DNA methyltransferase 1 (DNMT1) is the most abundantly known. But evidence supporting its role in skin aging remains scarce, and no report regards its specifical upstream-regulating molecules in the process of skin aging so far. Here, we found that DNMT1 expression was markedly higher in young human skin fibroblasts (HSFs) than that in passage-aged HSFs, and DNMT1 knockdown significantly induced the senescence phenotype in young HSFs. We predicted the upstream miRNAs which could regulate DNMT1 with miRNA databases and found miR-377 had high homology with a sequence in the 3′-UTR of human DNMT1 mRNA. We confirmed that miR-377 was a potential regulator of DNMT1 by luciferase reporter assays. miR-377 expression in passage-aged HSFs was markedly higher than that in the young HSFs. miR-377 overexpression promoted senescence in young HSFs, and inhibition of miR-377 reduced senescence in passage-aged HSFs. Moreover, these functions were mediated by targeting DNMT1. Microfluidic PCR and next-generation bisulfite sequencing of 24 senescent-associated genes’ promoters revealed alterations of the promoter methylation levels of FoxD3, p53, and UTF1 in HSFs treated with miR-377 mimics or inhibitors. We also verified that the miR-377-mediated changes in p53 expression could be reversed by regulation of DNMT1 in HSFs. Similarly, there was a negative correlation between miR-377 and DNMT1 expression in young and photoaged HSFs, HSFs, or skin tissues from UV-unexposed areas of different aged donors. Our results highlight a novel role for miR-377-DNMT1-p53 axis in HSF senescence. These findings shed new light on the mechanisms of skin aging and identify future opportunities for its therapeutic prevention.

scholarly journals Correction: miR-377 induces senescence in human skin fibroblasts by targeting DNA methyltransferase 1

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Hong-fu Xie ◽  
Ying-zi Liu ◽  
Rui Du ◽  
Ben Wang ◽  
Meng-ting Chen ◽  
...  
Keyword(s):  
Human Skin ◽  
Dna Methyltransferase ◽  
Skin Fibroblasts ◽  
Dna Methyltransferase 1 ◽  
Human Skin Fibroblasts ◽  
Methyltransferase 1

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals DNA Methylation Biphasically Regulates 3T3-L1 Preadipocyte Differentiation

2016 ◽  
Vol 30 (6) ◽  
pp. 677-687 ◽  
Author(s):  
Xiaosong Yang ◽  
Rui Wu ◽  
Weiguang Shan ◽  
Liqing Yu ◽  
Bingzhong Xue ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Late Stage ◽  
Dna Methyltransferase ◽  
Early Stage ◽  
Luciferase Reporter ◽  
Dna Methyltransferase 1 ◽  
Loss Of Function ◽  
Preadipocyte Differentiation ◽  
Treatment Of Obesity ◽  
Methyltransferase 1

Abstract Better understanding the mechanisms underlying adipogenesis may provide novel therapeutic targets in the treatment of obesity. Most studies investigating the mechanisms underlying adipogenesis focus on highly regulated transcriptional pathways; little is known about the epigenetic mechanisms in this process. Here, we determined the role of DNA methylation in regulating 3T3-L1 adipogenesis in early and late stage of differentiation. We found that inhibiting DNA methylation pharmacologically by 5-aza-2′-deoxycytidine (5-aza-dC) at early stage of 3T3-L1 differentiation markedly suppressed adipogenesis. This inhibition of adipogenesis by 5-aza-dC was associated with up-regulation of Wnt10a, an antiadipogenic factor, and down-regulation of Wnt10a promoter methylation. In contrast, inhibiting DNA methylation by 5-aza-dC at late stage of differentiation enhanced the lipogenic program. The differential effects of 5-aza-dC on adipogenesis were confirmed by gain or loss of function of DNA methyltransferase 1 using genetic approaches. We further explored the molecular mechanism underlying the enhanced lipogenesis by inhibition of DNA methylation at late stage of differentiation. The Srebp1c promoter is enriched with CpG sites. Chromatin immunoprecipitation assays showed that DNA methyltransferase 1 bound to the methylation region at the Srebp1c promoter. Pyrosequencing analysis revealed that the DNA methylation at the key cis-elements of the Srebp1c promoter was down-regulated in adipogenesis. Further, luciferase reporter assays showed that the Srebp1c promoter activity was dramatically up-regulated by the unmethylated promoter compared with the fully methylated promoter. Thus DNA methylation appears to exert a biphasic regulatory role in adipogenesis, promoting differentiation at early stage while inhibiting lipogenesis at late stage of 3T3-L1 preadipocyte differentiation.

scholarly journals Exosomal MiR-769-5p Exacerbates Ultraviolet-Induced Bystander Effect by Targeting TGFBR1

2020 ◽  
Vol 11 ◽  
Author(s):  
Na Ni ◽  
Weiwei Ma ◽  
Yanling Tao ◽  
Juan Liu ◽  
Hui Hua ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Human Skin ◽  
Bystander Effect ◽  
Transforming Growth Factor ◽  
Underlying Mechanism ◽  
Skin Fibroblasts ◽  
Luciferase Reporter ◽  
Human Skin Fibroblasts ◽  
Bystander Effects ◽  
Damage Level

Exosomal microRNAs have been investigated in bystander effect, but it is unclear whether microRNA works in ultraviolet radiation–induced bystander effects (UV-RIBEs) and what the underlying mechanism could be. Exosomes from ultraviolet (UV)–irradiated human skin fibroblasts (HSFs) were isolated and transferred to normal HSFs, followed by the detection of proliferation rate, oxidative damage level, and apoptosis rate. Exosomal miRNAs were evaluated and screened with miRNA sequencing and quantitative reverse transcriptase–polymerase chain reaction method. MiRNA shuttle and bystander photodamage reactions were observed after transfection of miR-769-5p. MiR-769-5p targeting gene transforming growth factor-β1 (TGFBR1), and TGFBR1 mRNA 3′-untranslated region (UTR) was assessed and identified by Western blotting and dual-luciferase reporter assay. Bystander effects were induced after being treated with isolated exosomes from UV-irradiated HSFs. Exosomal miR-769-5p expression was significantly upregulated. Human skin fibroblasts showed lower proliferation, increasing oxidative damage, and faster occurrence of apoptosis after transfection. Exosome-mediated transfer of miR-769-5p was observed. Upregulation of miR-769-5p induced bystander effects, whereas downregulation of miR-769-5p can suppress UV-RIBEs. In addition, miR-769-5p was found to downregulate TGFBR1 gene expression by directly targeting its 3′-UTR. Our results demonstrate that exosome-mediated miR-769-5p transfer could function as an intercellular messenger and exacerbate UV-RIBEs. MiR-769-5p inhibits the expression of TGFBR1 by targeting TGFBR1 mRNA 3′-UTR.

scholarly journals DNA Methylation by DNA Methyltransferase 1 Is Critical for Effector CD8 T Cell Expansion

2006 ◽  
Vol 176 (8) ◽  
pp. 4562-4572 ◽  
Author(s):  
Craig Chappell ◽  
Caroline Beard ◽  
John Altman ◽  
Rudolph Jaenisch ◽  
Joshy Jacob
Keyword(s):  
Dna Methylation ◽  
T Cell ◽  
Cell Expansion ◽  
Dna Methyltransferase ◽  
Cd8 T Cell ◽  
Dna Methyltransferase 1 ◽  
T Cell Expansion ◽  
Methyltransferase 1
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