Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes

Skin melanocytes harbor a complex photosensitive system comprised of opsins, which were shown, in recent years, to display light- and thermo-independent functions. Based on this premise, we investigated whether melanopsin, OPN4, displays such a role in normal melanocytes. In this study, we found tha...

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Bibliographic Details
Main Authors: Leonardo Vinícius Monteiro de Assis, Maria Nathália Moraes, Davi Mendes, Matheus Molina Silva, Carlos Frederico Martins Menck, Ana Maria de Lauro Castrucci
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/43/3/101
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Summary:Skin melanocytes harbor a complex photosensitive system comprised of opsins, which were shown, in recent years, to display light- and thermo-independent functions. Based on this premise, we investigated whether melanopsin, OPN4, displays such a role in normal melanocytes. In this study, we found that murine <i>Opn4</i><sup>KO</sup> melanocytes displayed a faster proliferation rate compared to <i>Opn4</i><sup>WT</sup> melanocytes. Cell cycle population analysis demonstrated that OPN4<sup>KO</sup> melanocytes exhibited a faster cell cycle progression with reduced G<sub>0</sub>–G<sub>1</sub><b>,</b> and highly increased S and slightly increased G<sub>2</sub>/M cell populations compared to the <i>Opn4</i><sup>WT</sup> counterparts. Expression of specific cell cycle-related genes in <i>Opn4</i><sup>KO</sup> melanocytes exhibited alterations that corroborate a faster cell cycle progression. We also found significant modification in gene and protein expression levels of important regulators of melanocyte physiology. PER1 protein level was higher while BMAL1 and REV-ERBα decreased in <i>Opn4</i><sup>KO</sup> melanocytes compared to <i>Opn4</i><sup>WT</sup> cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in <i>Opn4</i><sup>KO</sup> melanocytes, which is in line with a higher proliferative capability. Taken altogether, we demonstrated that OPN4 regulates cell proliferation, cell cycle, and affects the expression of several important factors of the melanocyte physiology; thus, arguing for a putative tumor suppression role in melanocytes.
ISSN:1467-3037
1467-3045