MicroRNAs in the skin: role in development, homoeostasis and regeneration

Horsburgh, Steven; Fullard, Nicola; Roger, Mathilde; Degnan, Abbie; Todryk, Stephen; Przyborski, Stefan; O’Reilly, Steven

doi:10.1042/cs20170039

Cited by 32 publications

(30 citation statements)

References 126 publications

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“…MicroRNAs are small noncoding RNAs that regulate specific target gene expression by repressing messenger RNA (mRNA) translation or by directly degrading mRNA . One microRNA is able to repress up to hundreds of genes, and one gene can be repressed by several microRNAs.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Fibroblast Apoptosis and Proliferation by MicroRNA‐125b in Systemic Sclerosis

Kozlova

Pachera

Maurer

et al. 2019

Arthritis & Rheumatology

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Objective. To analyze the expression, regulation, and role of microRNA-125b (miR-125b) in systemic sclerosis (SSc).Methods. MiR-125b expression was assessed by quantitative polymerase chain reaction (qPCR) of RNA from dermal fibroblasts and whole skin biopsy specimens from healthy controls and SSc patients. To identify downstream effectors, RNA from healthy control fibroblasts was sequenced after miR-125b knockdown and further validated using qPCR and Western blotting. Fibrosis, apoptosis, and proliferation were assessed by Caspase-Glo 3/7 assay, Western blotting, immunofluorescence staining for cleaved caspase 3, and annexin V real-time assay in dermal fibroblasts.Results. Expression of miR-125b was significantly down-regulated in SSc skin biopsy specimens by 53% (median fold change 0.47 [interquartile range 0.35-0.69]; P < 0.001) and in SSc dermal fibroblasts by 47% (median fold change 0.53 [interquartile range 0.36-0.58]; P < 0.001) compared to healthy control skin biopsy specimens and fibroblasts, respectively (n = 10 samples per group). Treatment with the histone deacetylase inhibitors trichostatin A and tubastatin A significantly decreased the expression of miR-125b in dermal fibroblasts. MiR-125b knockdown significantly reduced cell proliferation and α-smooth muscle actin (α-SMA) expression at the messenger RNA (mRNA) and protein levels. RNA-Seq identified BAK1, BMF, and BBC3 as potential targets of miR-125b. Quantitative PCR confirmed that knockdown of miR-125b up-regulated these genes (P < 0.01; n = 12). Bcl-2 homologous antagonist killer 1 showed the strongest induction confirmed at the protein level (P < 0.01; n = 10). Consequently, miR-125b knockdown increased apoptosis compared to scrambled control. Accordingly, miR-125b overexpression decreased apoptosis.Conclusion. Our findings indicate that miR-125b is down-regulated in SSc skin and primary dermal fibroblasts. MiR-125b down-regulation increases apoptosis and decreases proliferation and α-SMA expression in dermal fibroblasts, indicating that its compensatory, antifibrotic mechanism may be a potential novel therapeutic option.

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Section: Introductionmentioning

confidence: 99%

Regulation of Fibroblast Apoptosis and Proliferation by MicroRNA‐125b in Systemic Sclerosis

Kozlova

Pachera

Maurer

et al. 2019

Arthritis & Rheumatology

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“…microRNAs (miRNAs) are small 20 to 25 nucleotides long non‐coding RNAs that modulate gene expression on the epigenetic level . Since their discovery in 1993, a large number of studies have proven the importance of miRNAs for the regulation of tissue development and cellular function, including cell survival, proliferation and cell fate determination . In the recent years, it has been discovered that miRNAs can act not only in the cell in which they are produced, but can also be delivered to adjacent cells, inducing gene regulatory effects therein .…”

Section: Introductionmentioning

confidence: 99%

Potential mechanisms of microRNA mobility

Lemcke

Dávid

2018

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microRNAs (miRNAs) are important epigenetic modulators of gene expression that control cellular physiology as well as tissue homeostasis, and development. In addition to the temporal aspects of miRNA-mediated gene regulation, the intracellular localization of miRNA is crucial for its silencing activity. Recent studies indicated that miRNA is even translocated between cells via gap junctional cell-cell contacts, allowing spatiotemporal modulation of gene expression within multicellular systems. Although non coding RNA remains a focus of intense research, studies regarding the intra-and intercellular mobility of small RNAs are still largely missing. Emerging data from experimental and computational work suggest the involvement of transport mechanisms governing proper localization of miRNA in single cells and cellular syncytia. Based on these data, we discuss a model of miRNA translocation that could help to address the spatial aspects of miRNA function and the impact of miRNA molecules on the intercellular signaling network.

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“…Recent studies demonstrated that the expression profiles of miRNA showed tissue-specific expression patterns in the epidermis hair follicles, stage-specific expression in the periodic development of hair follicles as well as pigmentation [26][27][28]. miRNAs in different cell types form a comprehensive, multi-level network system through interactions with signal pathway and regulation factors [29,30]. In this study, the GO terms of the target genes of differentially expressed miRNAs in black coat color skin are mainly enriched in the nucleus of its cellular component, chromatin binding metal ion binding in molecular function, positive regulation of transcription from RNA polymerase promoter, and negative regulation of transcription from RNA polymerase promoter in biological process.…”

Section: Discussionmentioning

confidence: 99%

The comprehensive detection of miRNA, lncRNA, and circRNA in regulation of mouse melanocyte and skin development

Zhu

et al. 2020

Biol Res

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Background: Pigmentation development, is a complex process regulated by many transcription factors during development. With the development of the RNA sequencing (RNA-seq), non-coding RNAs, such as miRNAs, lncRNAs, and circRNAs, are found to play an important role in the function detection of related regulation factors. In this study, we provided the expression profiles and development of ncRNAs related to melanocyte and skin development in mice with black coat color skin and mice with white coat color skin during embryonic day 15 (E15) and postnatal day 7 (P7). The expression profiles of different ncRNAs were detected via RNA-seq and also confirmed by the quantitative real-time PCR (qRT-PCR) method. GO and KEGG used to analyze the function the related target genes. Results:We identified an extensive catalogue of 206 and 183 differently expressed miRNAs, 600 and 800 differently expressed lncRNAs, and 50 and 54 differently expressed circRNAs, respectively. GO terms and pathway analysis showed the target genes of differentially expressed miRNA and lncRNA. The host genes of circRNA were mainly enriched in cellular process, single organism process. The target genes of miRNAs were mainly enriched in chromatin binding and calcium ion binding in the nucleus. The function of genes related to lncRNAs are post translation modification. The competing endogenous RNA (ceRNA) network of lncRNAs and circRNAs displays a complex interaction between ncRNA and mRNA related to skin development, such as Tcf4, Gnas, and Gpnms related to melanocyte development. Conclusions:The ceRNA network of lncRNA and circRNA displays a complex interaction between ncRNA and mRNA related to skin development and melanocyte development. The embryonic and postnatal development of skin provide a reference for further studies on the development mechanisms of ncRNA during pigmentation.

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MicroRNAs in the skin: role in development, homoeostasis and regeneration

Cited by 32 publications

References 126 publications

Regulation of Fibroblast Apoptosis and Proliferation by MicroRNA‐125b in Systemic Sclerosis

Regulation of Fibroblast Apoptosis and Proliferation by MicroRNA‐125b in Systemic Sclerosis

Potential mechanisms of microRNA mobility

The comprehensive detection of miRNA, lncRNA, and circRNA in regulation of mouse melanocyte and skin development

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