Our previous work has identified miR-125b as a negative regulator of melanogenesis. However, the specific melanogenesis-related genes targeted by this miRNA had not been identified. In this study, we established a screening strategy involving three consecutive analytical approaches—analysis of target genes of miR-125b, expression correlation analysis between each target gene and representative pigmentary genes, and functional analysis of candidate genes related to melanogenesis—to discover melanogenesis-related genes targeted by miR-125b. Through these analyses, we identified SRC homology 3 domain-binding protein 4 (SH3BP4) as a novel pigmentation gene. In addition, by combining bioinformatics analysis and experimental validation, we demonstrated that SH3BP4 is a direct target of miR-125b. Finally, we found that SH3BP4 is transcriptionally regulated by microphthalmia-associated transcription factor as its direct target. These findings provide important insights into the roles of miRNAs and their targets in melanogenesis.
Computational Biology ; Mass Screening ; Microphthalmia-Associated Transcription Factor ; MicroRNAs ; Pigmentation*

Melanogenesis is a biosynthetic pathway to produce melanin pigment in melanocyte, involving a series of intricate enzymatic and chemical catalyzed reactions. Melanogenesis involves five signaling pathways that converge on microphthalmia-associated transcription factor. In addition, many cytokines, involved in the regulation of melanogenesis, play an important role in the development, proliferation, differentiation and migration of melanocytes. Polyoxometalate can be used as a potential inhibitor of melanin production. Hence, this paper reviews the signaling pathways of melanogenesis and their regulatory mechanism, to apply polyoxometalates in the melanin production pathway, and briefly introduces the regulatory factors of related pathways.
Cell Differentiation ; Melanins ; Melanocytes ; Microphthalmia-Associated Transcription Factor ; Signal Transduction

UNLABELLEDObjectiive：To explore the effect of miR137 target gene MITF on the prognosis of multiple myeloma (MM).

METHODSThe target genes of miR137 were predicted by software, the GFP analysis was carried out for detecting MITF as the prognosis of multiple myeloma. The cell line overexpressing miR137 in MM cell line was constructed. Real-time qPCR and Western blot were used to detect the expression of MITF in this cell line.

RESULTSThe target genes of miR137 were MITF, BUE2H, SH3BP5 and KLF12. High expression of MITF in MM patients showed a good prognosis according to GFP analysis, but no significant difference was detected between the different subgroups. MITF expression was higher in MM cell line that over expressed miR137.

CONCLUSIONThe miR137-MITF is an important index in judging the prognosis of multiple myeloma.

Adolescent ; Humans ; Male ; Microphthalmia-Associated Transcription Factor ; genetics ; Mutation ; Waardenburg Syndrome ; genetics

Fucoidan, a fucose-rich sulfated polysaccharide derived from brown seaweed in the class Phaeophyceae, has been widely studied for its possible health benefits. However, the potential of fucoidan as a possible treatment for hyperpigmentation is not fully understood. This study investigated the effects of fucoidan on melanogenesis and related signaling pathways using Mel-Ab cells. Fucoidan significantly decreased melanin content. While fucoidan treatment decreased tyrosinase activity, it did not do so directly. Western blot analysis indicated that fucoidan downregulated microphthalmia-associated transcription factor and reduced tyrosinase protein expression. Further investigation showed that fucoidan activated the extracellular signal-regulated kinase (ERK) pathway, suggesting a possible mechanism for the inhibition of melanin synthesis. Treatment with PD98059, a specific ERK inhibitor, resulted in the recovery of melanin production. Taken together, these findings suggest that fucoidan inhibits melanogenesis via ERK phosphorylation.
Blotting, Western ; Hyperpigmentation ; Insurance Benefits ; Melanins ; Microphthalmia-Associated Transcription Factor ; Monophenol Monooxygenase ; Phaeophyta ; Phosphorylation ; Phosphotransferases ; Seaweed

OBJECTIVETo explore the molecular mechanism of Waardenburg syndrome type II (WS2) resulting from SOX10 gene mutation E248fs through in vitro experiment.

METHODS293T cells were transiently transfected with wild type (WT) SOX10 and mutant type (MT) E248fs plasmids. The regulatory effect of WT/MT SOX10 on the transcriptional activity of MITF gene and influence of E248fs on WT SOX10 function were determined with a luciferase activity assay. The DNA binding capacity of the WT/MT SOX10 with the promoter of the MITF gene was determined with a biotinylated double-stranded oligonucleotide probe containing the SOX10 binding sequence cattgtc to precipitate MITF and E248fs, respectively. The stability of SOX10 and E248fs were also analyzed.

RESULTSAs a loss-of-function mutation, the E248fs mutant failed to transactivate the MITF promoter as compared with the WT SOX10 (P<0.01), which also showed a dominant-negative effect on WT SOX10. The WT SOX10 and E248fs mutant were also able to bind specifically to the cattgtc motif in the MITF promoter, whereas E248fs had degraded faster than WT SOX10.

CONCLUSIONDespite the fact that the E248fs has a dominant-negative effect on SOX10, its reduced stability may down-regulate the transcription of MITF and decrease the synthesis of melanin, which may result in haploinsufficiency of SOX10 protein and cause the milder WS2 phenotype.

Resveratrol is a polyphenolic compound found in various natural products such as grapes and berries and possesses anti-cancer, anti-hyperlipidemia, and anti-aging properties. Recently, it has been reported that resveratrol inhibits alpha-melanocyte-stimulating hormone signaling, viability, and migration in melanoma cells. However, these effects have not been confirmed in vivo, specifically brownish guinea pigs. To evaluate the potential of resveratrol as a regulator of melanin for hyperpigmentation therapy, the influence of resveratrol on pigmentation was investigated by ultraviolet B-induced hyperpigmentation in brownish guinea pig skin. We found that resveratrol reduced the expression of melanogenesis-related proteins tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor in melanoma cells. Furthermore, topical application of resveratrol was demonstrated to significantly decrease hyperpigmentation on ultraviolet B-stimulated guinea pig skin in vivo. Based on our histological data, resveratrol inhibits melanin synthesis via a reduction in tyrosinase-related protein 2 among the melanogenic enzymes. This study is the first to provide evidence supporting resveratrol as a depigmentation agent, along with further clinical investigation of resveratrol in ultraviolet B-induced skin disorders such as hyperpigmentation and skin photoaging.
alpha-MSH ; Animals ; Biological Products ; Fruit ; Guinea Pigs* ; Hyperpigmentation ; Melanins* ; Melanoma ; Microphthalmia-Associated Transcription Factor ; Monophenol Monooxygenase ; Pigmentation* ; Skin* ; Vitis

Resveratrol is a polyphenolic compound found in various natural products such as grapes and berries and possesses anti-cancer, anti-hyperlipidemia, and anti-aging properties. Recently, it has been reported that resveratrol inhibits alpha-melanocyte-stimulating hormone signaling, viability, and migration in melanoma cells. However, these effects have not been confirmed in vivo, specifically brownish guinea pigs. To evaluate the potential of resveratrol as a regulator of melanin for hyperpigmentation therapy, the influence of resveratrol on pigmentation was investigated by ultraviolet B-induced hyperpigmentation in brownish guinea pig skin. We found that resveratrol reduced the expression of melanogenesis-related proteins tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor in melanoma cells. Furthermore, topical application of resveratrol was demonstrated to significantly decrease hyperpigmentation on ultraviolet B-stimulated guinea pig skin in vivo. Based on our histological data, resveratrol inhibits melanin synthesis via a reduction in tyrosinase-related protein 2 among the melanogenic enzymes. This study is the first to provide evidence supporting resveratrol as a depigmentation agent, along with further clinical investigation of resveratrol in ultraviolet B-induced skin disorders such as hyperpigmentation and skin photoaging.
alpha-MSH ; Animals ; Biological Products ; Fruit ; Guinea Pigs* ; Hyperpigmentation ; Melanins* ; Melanoma ; Microphthalmia-Associated Transcription Factor ; Monophenol Monooxygenase ; Pigmentation* ; Skin* ; Vitis

BACKGROUND: Bacteria associated with marine invertebrates are a rich source of bioactive metabolites. OBJECTIVE: The effects of marine bacteria extracts on pigmentation were investigated to find novel whitening agents. METHODS: The marine bacteria collected near Gangwha Island in Korea were isolated and extracted using organic solvent. The organic extracts were screened and selected using the cell free tyrosinase activity. The whitening effects of the selected extract were further investigated using cultured melanocytes, cultured skin and in vivo zebrafish. The whitening mechanism of the marine extract was also investigated. RESULTS: The marine bacterial methylene chloride extract reduced the pigmentation of Melan-a cells, human melanocytes, cultured skin and in vivo zebrafish. The decrease in pigmentation was due to the inhibition of tyrosinase activity and the expression of tyrosinase and microphthalmia-associated transcription factor protein. These bacteria were identified as a novel Pseudomonas species. CONCLUSION: The methylene chloride extract of marine pseudomonas species possesses a whitening effect. Further chemical isolation and characterization of the active compounds from this marine bacterial extract are needed.
Bacteria ; Humans ; Invertebrates ; Korea ; MART-1 Antigen ; Melanocytes ; Methylene Chloride ; Microphthalmia-Associated Transcription Factor ; Monophenol Monooxygenase ; Pigmentation ; Pseudomonas ; Skin ; Zebrafish

BACKGROUND: A number of cytokines, growth factors and inflammatory mediators made by keratinocytes, fibroblasts and potentially other cells in the skin were shown to augment melanin production and/or melanin transfer to keratinocytes. A lot of studies were done to investigate the mechanisms. But there was no studies about sequential relationship between the suggestive factors. OBJECT: To measure the changes in expressions of ET-1, MITF, and PAR-2 after UV exposure on skin in Korean. MATERIAL AND METHOD: We established an immunohistochemical staining protocol for specimens which were obtained from UV-irradiated skin in four healthy Korean males on the 2nd, 4th, 7th days after UV irradiation. RESULT: This study reveals the sequential relationship between ET-1, MITF, and PAR-2. ET-1 was increased at day 2 and decreased at day 4 and 7. MITF increased gradually day 2, day 4, and day 7. PAR-2 increased at day 4 and increased once more at day 7.
Cytokines ; Endothelin-1* ; Fibroblasts ; Humans ; Intercellular Signaling Peptides and Proteins ; Keratinocytes ; Male ; Melanins ; Melanocytes ; Microphthalmia-Associated Transcription Factor* ; Microphthalmos* ; Skin