MicroRNA-155 is Dysregulated in the Skin of Patients with Vitiligo and Inhibits Melanogenesis-associated Genes in Melanocytes and Keratinocytes

Šahmatova, Liisi; Tankov, Stoyan; Prans, Ele; Aab, Alar; Hermann, Helen; Reemann, Paula; Pihlap, Maire; Karelson, Maire; Abram, Kristi; Kisand, Kai; Kingo, Külli; Rebane, Ana

doi:10.2340/00015555-2394

Cited by 38 publications

(53 citation statements)

References 59 publications

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“…As miR-146a/b have similar expression level in vivo in human and mouse skin, miR-146a/b together might have remarkably stronger influence than studies performed with miR-146a−/− mice demonstrate. On the other hand, the observation that the expression of miR-146a/b in normal skin and psoriatic lesions is 10-50-fold lower than that of the most highly expressed miR-203 and miR-125b further supports the therapeutic potential of miR-146a/b overexpression (Lovendorf et al , 2015; Sahmatova et al , 2016). …”

Section: Discussionmentioning

confidence: 87%

miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

Hermann

Runnel

Aab

et al. 2017

Journal of Investigative Dermatology

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miR-146a inhibits inflammatory responses in human keratinocytes and in different mouse models of skin inflammation. Little is known about the role of miR-146b in the skin. In the present study, we confirmed the increased expression of miR-146a and miR-146b (miR-146a/b) in lesional skin of psoriasis patients. The expression of miR-146a was about 2-fold higher than that of miR-146b in healthy human skin and it was more strongly induced by stimulation of pro-inflammatory cytokines in keratinocytes and fibroblasts. miR-146a/b target genes regulating inflammatory responses or proliferation were altered in the skin of psoriasis patients, among which FERMT1 was verified as direct target of miR-146a. In silico analysis of genome-wide data from >4,000 psoriasis cases and >8,000 controls confirmed a moderate association between psoriasis and genetic variants in miR-146a gene. Transfection of miR-146a/b suppressed and inhibition enhanced keratinocyte proliferation and the expression of psoriasis-related target genes. Enhanced expression of miR-146a/b-influenced genes was detected in cultured keratinocytes from miR-146a−/− and skin fibroblasts from miR-146a−/− and miR-146b−/− mice stimulated with psoriasis-associated cytokines as compared to wild type mice. Our results indicate that besides miR-146a, miR-146b is expressed and might be capable of modulation of inflammatory responses and keratinocyte proliferation in psoriatic skin.

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Section: Discussionmentioning

confidence: 87%

miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

Hermann

Runnel

Aab

et al. 2017

Journal of Investigative Dermatology

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“…Dysregulated miRNA expression is associated with the pathogenesis of various inflammatory skin disorders such as psoriasis, atopic dermatitis, and allergic contact dermatitis (Sonkoly E et al , 2008), and there is some evidence implicating miRNAs in vitiligo. Gene expression microarray studies have revealed aberrant miRNA expression in the skin and serum of patients with vitiligo (Mansuri et al , 2014, Shi et al , 2014, Shi et al , 2013), with upregulation of miR-224-3p, miR-4712-3p, and miR-3940-5p in peripheral blood mononuclear cells (Wang et al , 2015), miR-25 upregulated in serum (Shi et al , 2016) and miR-99b, miR-125-b, miR-155, and miR-199a-3p upregulated in the skin (Šahmatova et al , 2016) of vitiligo patients. Little is known, however, about the exact role of miRNAs, their targets, and their mechanism of action in the pathophysiology of vitiligo.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo

Sahoo

Lee

Boniface

et al. 2017

Journal of Investigative Dermatology

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Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing (RNA-seq), targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched miR-211, a known metabolic switch in non-pigmented melanoma cells, was severely downregulated in vitiligo cell line PIG3V and skin biopsies from vitiligo patients, while its predicted targets transcriptional co-activator PGC1-α (PPARGC1A), ribonucleotide reductase regulatory subunit M2 (RRM2), and serine-threonine protein kinase TAO1 (TAOK1) were reciprocally upregulated. miR-211 binds to PGC1-α 3’UTR locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated miR-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of miR-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.

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“…miR-202 inhibits tumor progression and (Farhana et al, 2015;Lin et al, 2016;Meng et al, 2016) affects the immune system (Fornari et al, 2015;Owen et al, 2015). miRNAs regulate levels of expression of target genes by controlling the signal pathways (Š ahmatova et al, 2016;Wang et al, 2016). Some target genes of miR-202 have a regulatory effect on coat color, and studies have shown that expression of the miR-202 target gene wnt5a is correlated with sensitivity to bio-and targeted therapies of melanoma (Tímár et al, 2006).…”

Section: Discussionmentioning

confidence: 97%

Differential Expression of miR-202 and Validation of Predicted Target Genes in the Skin Tissue of C57BL/6 Black Mice and BALB/c White Mice

Liu

Zhao

et al. 2017

DNA and Cell Biology

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In recent years, with the need of the fur industry to obtain greater quantities of high-quality fur and the research of hair follicle development attracting greater attention, the role of miRNAs in hair follicle development has become a field of intense interest. miRNAs are short length RNAs that affect gene regulation by binding to the 3'-untranslated region (3'UTR) of the mRNAs of certain target genes. This study predicted and validated the target genes of miR-202 in the skin tissue of C57BL/6 black mice and BALB/c white mice. The expression of miR-202 target genes (wnt5a, kit, and tcf7) was examined by real-time quantitative polymerase chain reaction and western blot in the mouse skin tissue and human embryonic kidney 293T cells (HEK293T cells) which overexpress miR-202. The luciferase reporter gene system was used to verify the correlation between the expression of miR-202 and its putative target genes. We show that the expression of miR-202 was higher in the skin tissue of C57BL/6 black mice than in the skin tissue of BALB/c white mice (p < 0.05). Furthermore, the expression of wnt5a, kit, and tcf7 was observed to be negatively correlated with the expression of miR-202 and to be downregulated by miR-202 in vitro and in vivo. The luciferase reporter gene system indicated that the target sequences of miR-202 are present in 3'UTR of wnt5a, kit, and tcf7 mRNAs. Altogether, this study has shown that the expression of miR-202 was different in the skin tissue of C57BL/6 black mice and BALB/c white mice and that wnt5a, kit, and tcf7 are negatively regulated by miR-202.

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MicroRNA-155 is Dysregulated in the Skin of Patients with Vitiligo and Inhibits Melanogenesis-associated Genes in Melanocytes and Keratinocytes

Cited by 38 publications

References 59 publications

miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

miR-146b Probably Assists miRNA-146a in the Suppression of Keratinocyte Proliferation and Inflammatory Responses in Psoriasis

MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo

Differential Expression of miR-202 and Validation of Predicted Target Genes in the Skin Tissue of C57BL/6 Black Mice and BALB/c White Mice

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