Micro<scp>RNA</scp>s in melanocyte and melanoma biology

Mione, Marina; Bosserhoff, Anja‐Katrin

doi:10.1111/pcmr.12346

Cited by 53 publications

(55 citation statements)

References 154 publications

(186 reference statements)

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“…Thus, it is possible that loss of miRNAs in melanocytes could cause pigmentary changes resulting in alterations in coat color. Indeed, several melanocyte miRNAs are linked to either melanocyte survival or pigmentation processes (47)(48)(49)(50)(51). Therefore, we hypothesized that the link between coat color and the severity of retinal degeneration might arise from Cre expression patterns that vary from animal to animal but remain consistent within the pigmentary cells of the same animal.…”

Section: Maturementioning

confidence: 99%

MicroRNA-processing Enzymes Are Essential for Survival and Function of Mature Retinal Pigmented Epithelial Cells in Mice

Sundermeier¹,

Sakami²,

Sahu

et al. 2017

Journal of Biological Chemistry

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Edited by Paul E. FraserAge-related macular degeneration (AMD) is a major cause of irreversible vision loss. The neovascular or "wet" form of AMD can be treated to varying degrees with anti-angiogenic drugs, but geographic atrophy (GA) is an advanced stage of the more prevalent "dry" form of AMD for which there is no effective treatment. Development of GA has been linked to loss of the microRNA (miRNA)-processing enzyme DICER1 in the mature retinal pigmented epithelium (RPE). This loss results in the accumulation of toxic transcripts of Alu transposable elements, which activate the NLRP3 inflammasome and additional downstream pathways that compromise the integrity and function of the RPE. However, it remains unclear whether the loss of miRNA processing and subsequent gene regulation in the RPE due to DICER1 deficiency also contributes to RPE cell death. To clarify the role of miRNAs in RPE cells, we used two different mature RPE cell-specific Cre recombinase drivers to inactivate either Dicer1 or DiGeorge syndrome critical region 8 (Dgcr8), thus removing RPE miRNA regulatory activity in mice by disrupting two independent and essential steps of miRNA biogenesis. In contrast with prior studies, we found that the loss of each factor independently led to strikingly similar defects in the survival and function of the RPE and retina. These results suggest that the loss of miRNAs also contributes to RPE cell death and loss of visual function and could affect the pathology of dry AMD. Age-related macular degeneration (AMD)3 is a progressive retinal degenerative disorder that preferentially impacts the macula, the central region of the retina primarily responsible for both color vision and visual acuity. AMD is the leading cause of irreversible vision loss in modern Western societies among adults over 50 and is projected to impact the lives of nearly 200 million people worldwide by the year 2020 (1-4). It presents in two distinct forms, based on the types of lesions that occur in the late stages. The neovascular or "wet" form of AMD is associated with abnormal growth of blood vessels in the choriocapillaris, which extend through Bruch's membrane and cause acute vision loss that can be reversed relatively rapidly through intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors (5-8). In contrast, the dry form of AMD is characterized by a large number of drusen and occasionally by geographic atrophy (GA), the regional loss of macular photoreceptors, retinal pigmented epithelium (RPE), and choriocapillaris. These changes cause deficits in dark adaptation, along with dense visual field scotomas and a gradual decline in visual acuity (9 -11). Currently, there is no effective treatment for the dry form of AMD.Discovered over 2 decades ago in Caenorhabditis elegans, miRNAs regulate gene expression at the post-transcriptional level (12, 13). miRNA biogenesis involves two sequential cleavage steps. The first is accomplished in the nucleus by the microprocessor complex and involves a member of the ribonucleas...

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Section: Maturementioning

confidence: 99%

MicroRNA-processing Enzymes Are Essential for Survival and Function of Mature Retinal Pigmented Epithelial Cells in Mice

Sundermeier¹,

Sakami²,

Sahu

et al. 2017

Journal of Biological Chemistry

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“…Taken together, these data support the hypothesis that miR‐143‐5p regulates TAK1 expression. A previous study on miR‐143‐5p function in melanogenesis demonstrated that miR‐143‐5p expression was significantly lower in melanoma tissues compared to normal skin . Therefore, we also analysed miR‐143‐5p expression in alpaca skin and cultured melanocytes (Figure A and Figure ), further suggesting that miR‐143‐5p may play a role in regulating melanogenesis.…”

Section: Discussionmentioning

confidence: 87%

“…Cellular miRNA levels are tightly controlled through the process of maturation, which consequently affects target recognition . There is a growing number of identified miRNAs that regulate molecular pathways involved in melanocyte biology by targeting the relevant genes .…”

Section: Discussionmentioning

confidence: 99%

“…miR‐143 has been shown to play a role in embryonic stem cell (ESC) pluripotency by targeting Krüppel‐like factor 4 (KLF4), sex‐determining region Y‐box 2 (SOX2) and octamer‐binding transcription factor 4 (OCT4), suggesting that it facilitates ESC differentiation to distinct cell lineages, including neural crest cells. Moreover, miR‐143 is strongly associated with postrecurrence survival of metastatic melanoma patients, as its levels are significantly lower in melanoma tissues compared to normal skin . One of the predicted miR‐143‐5p targets is TAK1, a member of the mitogen‐activated protein kinase kinase kinase (MAPKKK) family .…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA 143‐5p regulates alpaca melanocyte migration, proliferation and melanogenesis

Zhang

et al. 2018

Experimental Dermatology

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microRNAs (miRNAs) have been shown to be closely involved in the control of melanogenesis and hair colour in mammals. Previous data also indicate that miR-143 regulates cell growth in melanoma. Here, we aimed to investigate the role of miR-143-5p in alpaca melanocytes. We found that miR-143-5p was highly expressed in the cytoplasm of alpaca melanocytes as demonstrated by an in situ hybridization assay. Prediction analysis revealed that miR-143-5p could regulate TGF-β-activated kinase 1 (TAK1) expression, which we confirmed by luciferase reporter assay, indicating that miR-143-5p controls TAK1 expression by directly targeting its 3' untranslated region (UTR). miR-143-5p overexpression decreased TAK1 expression, which led to increased melanocyte migration and proliferation, and downregulation of microphthalmia-associated transcription factor (MITF), which regulates melanin production. These results support a functional role for miR-143-5p in regulating alpaca melanocyte migration, proliferation and melanogenesis through direct targeting of TAK1.

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“…In this study, we have identified novel targets of miR‐214 and show that downregulation of these targets promotes malignant phenotype of melanoma cells. It is now well established that microRNAs play important roles in cancer including melanoma . β‐catenin, the critical component of Wnt signaling pathway, has been shown to be regulated by miR‐214 .…”

Section: Discussionmentioning

confidence: 99%

Role of miR‐214 in regulation of β‐catenin and the malignant phenotype of melanoma

Prabhakar

Rodríguez

Jayanthy

et al. 2019

Molecular Carcinogenesis

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Wnt/β‐catenin signaling plays an important role in melanocyte biology, especially in the early stages of melanocyte transformation and melanomagenesis. β‐catenin, encoded by the gene CTNNB1, is an intracellular signal transducer of Wnt signaling and activates transcription of genes important for cell proliferation and survival. Wnt/β‐catenin signaling is frequently activated in melanoma through oncogenic mutations of β‐catenin and elevated β‐catenin levels are positively correlated with melanoma aggressiveness. Molecular mechanisms that regulate β‐catenin expression in melanoma are not fully understood. MicroRNA‐214 is known to function as a tumor suppressor by targeting β‐catenin in several types of cancer cells. Here, we investigated the regulation of β‐catenin by miR‐214 and its role in melanoma. We show that β‐catenin mRNA levels are negatively correlated with miR‐214 in melanoma. However, overexpression of miR‐214 paradoxically increased β‐catenin protein levels and promoted malignant properties of melanoma cells including resistance to mitogen‐activated protein kinase inhibitors (MAPKi). RNA‐seq analysis revealed that melanoma cells predominantly express a β‐catenin mRNA isoform lacking miR‐214 target site. Using matched miRNA and mRNA‐seq and bioinformatics analysis, we identified novel miR‐214 targets, ankyrin repeat domain 6 (ANKRD6) and C‐terminal binding protein 1 (CTBP1), that are involved in negative regulation of Wnt signaling. Overexpression of miR‐214 or knockdown of the novel miR‐214 targets, ANKRD6 or CTBP1, increased melanoma cell proliferation, migration, and decreased sensitivity to MAPKi. Our data suggest that in melanoma cells β‐catenin is not regulated by miR‐214 and the functions of miR‐214 in melanoma are mediated partly by regulating proteins involved in attenuation of Wnt/β‐catenin signaling.

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MicroRNAs in melanocyte and melanoma biology

Cited by 53 publications

References 154 publications

MicroRNA-processing Enzymes Are Essential for Survival and Function of Mature Retinal Pigmented Epithelial Cells in Mice

MicroRNA-processing Enzymes Are Essential for Survival and Function of Mature Retinal Pigmented Epithelial Cells in Mice

MicroRNA 143‐5p regulates alpaca melanocyte migration, proliferation and melanogenesis

Role of miR‐214 in regulation of β‐catenin and the malignant phenotype of melanoma

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