Macrophage-derived soluble factor enhances melanoma inhibitory activity expression by uveal melanoma cells in vitro

This study explored the effects of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the development of uveal melanoma. Moreover, the role of the MALAT1/microRNA-608 (miR-608)/homeobox C4 (HOXC4) axis was assessed by evaluating the proliferation, invasion, and migration, as well as the cell cycle distribution of uveal melanoma in vitro after knocking down MALAT1 or HOXC4 and/or overexpression of miR-608 in uveal melanoma cells (MUM-2B and C918). Moreover, the effects of the MALAT1/miR-608/HOXC4 axis in uveal melanoma in vivo were further evaluated by injecting the C918 cells into the NOD/SCID mice. HOXC4 was found to be a gene upregulated in uveal melanoma, while knockdown of its expression resulted in suppression of uveal melanoma cell migration, proliferation, and invasion, as well as cell cycle progression. In addition, the upregulation of miR-608 reduced the expression of HOXC4 in the uveal melanoma cells, which was rescued by overexpression of MALAT1. Hence, MALAT1 could upregulate the HOXC4 by binding to miR-608. The suppressed progression of uveal melanoma in vitro by miR-608 was rescued by overexpression of MALAT1. Additionally, in vivo assays demonstrated that downregulation of MALAT1 could suppress tumor growth through downregulation of HOXC4 expression via increasing miR-608 in uveal melanoma. In summary, MALAT1 downregulation functions to restrain the development of uveal melanoma via miR-608-mediated inhibition of HOXC4.

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Upregulation of HMG1 Leads to Melanoma Inhibitory Activity Expression in Malignant Melanoma Cells and Contributes to Their Malignancy Phenotype

Molecular and Cellular Biology ◽

10.1128/mcb.23.8.2991-2998.2003 ◽

2003 ◽

Vol 23 (8) ◽

pp. 2991-2998 ◽

Cited By ~ 74

Author(s):

Ina Poser ◽

Michaela Golob ◽

Reinhard Buettner ◽

Anja K. Bosserhoff

Keyword(s):

Transcription Factor ◽

Malignant Melanoma ◽

Inhibitory Activity ◽

Melanoma Cells ◽

Peptide Sequence ◽

Transcriptional Level ◽

Promoter Element ◽

Promoter Activation ◽

Mobility Shift ◽

Melanoma Inhibitory Activity

ABSTRACT Malignant transformation of melanocytes to melanoma cells closely parallels activation of melanoma inhibitory activity (MIA) expression. We have previously shown that upregulation of MIA occurs on a transcriptional level and involves the highly conserved region (HCR) promoter element. We further observed that the HCR element interacts with the melanoma-associated transcription factor (MATF) and thereby confers strong promoter activation. In this study we identify the peptide sequence of MATF and show that it is identical with the transcription factor HMG1. HMG1 was upregulated in malignant melanoma cells and further activated by hypophosphorylation. Stable antisense-HMG1 expression in melanoma cells led to the reduction of MIA promoter activity and protein expression, indicating that HMG1 is a potent regulator of MIA expression. Interestingly, chromatin immunoprecipitation and electrophoretic mobility shift experiments indicated that HMG1 and the NF-κB family member p65 both interact and bind to the HCR promoter element. In summary, our study proves HMG1 and p65 to be important factors in MIA regulation and melanoma progression.

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Overexpression of melanoma inhibitory activity (MIA) enhances extravasation and metastasis of A-mel 3 melanoma cells in vivo

British Journal of Cancer ◽

10.1054/bjoc.2000.1424 ◽

2000 ◽

Vol 83 (9) ◽

pp. 1216-1222 ◽

Cited By ~ 44

Author(s):

M Guba ◽

A-K Bosserhoff ◽

M Steinbauer ◽

C Abels ◽

M Anthuber ◽

...

Keyword(s):

Inhibitory Activity ◽

Melanoma Cells ◽

Melanoma Inhibitory Activity

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Artocarpus Plants as a Potential Source of Skin Whitening Agents

Natural Product Communications ◽

10.1177/1934578x1100600943 ◽

2011 ◽

Vol 6 (9) ◽

pp. 1934578X1100600 ◽

Cited By ~ 7

Author(s):

Enos Tangke Arung ◽

Kuniyoshi Shimizu ◽

Ryuichiro Kondo

Keyword(s):

Inhibitory Activity ◽

Melanoma Cells ◽

B16 Melanoma ◽

Vitro Assay ◽

Skin Whitening ◽

Melanin Formation ◽

B16 Melanoma Cells ◽

Structure Activity

Artocarpus plants have been a focus of constant attention due to the potential for skin whitening agents. In the in vitro experiment, compounds from the Artocarpus plants, such as artocarpanone, norartocarpetin, artocarpesin, artogomezianol, andalasin, artocarbene, and chlorophorin showed tyrosinase inhibitory activity. Structure-activity investigations revealed that the 4-substituted resorcinol moiety in these compounds was responsible for their potent inhibitory activities on tyrosinase. In the in vitro assay, using B16 melanoma cells, the prenylated polyphenols isolated from Artocarpus plants, such as artocarpin, cudraflavone C, 6-prenylapigenin, kuwanon C, norartocarpin, albanin A, cudraflavone B, and brosimone I showed potent inhibitory activity on melanin formation. Structure-activity investigations revealed that the introduction of an isoprenoid moiety to a non-isoprenoid-substituted polyphenol enhanced the inhibitory activity of melanin production in B16 melanoma cells. In the in vivo investigation, the extract of the wood of Artocarpus incisus and a representative isolated compound from it, artocarpin had a lightening effect on the skin of guinea pigs’ backs. Other in vivo experiments using human volunteers have shown that water extract of Artocarpus lakoocha reduced the melanin formation in the skin of volunteers. These results indicate that the extracts of Artocarpus plants are potential sources for skin whitening agents.

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Effects of interferon alfa and gamma on human uveal melanoma cells in vitro.

British Journal of Ophthalmology ◽

10.1136/bjo.79.9.847 ◽

1995 ◽

Vol 79 (9) ◽

pp. 847-855 ◽

Cited By ~ 14

Author(s):

I de Waard-Siebinga ◽

W M Creyghton ◽

J Kool ◽

M J Jager

Keyword(s):

Uveal Melanoma ◽

Melanoma Cells ◽

Interferon Alfa

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HLA antigen expression on uveal melanoma cells in vivo and in vitro

Human Immunology ◽

10.1016/0198-8859(95)00083-g ◽

1995 ◽

Vol 44 (2) ◽

pp. 111-117 ◽

Cited By ~ 5

Author(s):

Itte de Waard-Siebinga ◽

Jeanette Kool ◽

Martine J. Jager

Keyword(s):

Uveal Melanoma ◽

Antigen Expression ◽

Melanoma Cells ◽

Hla Antigen

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The Anti-malarial Drug Artesunate Blocks Wnt/β-catenin Pathway and Inhibits Growth, Migration and Invasion of Uveal Melanoma Cells

Current Cancer Drug Targets ◽

10.2174/1568009618666180425142653 ◽

2018 ◽

Vol 18 (10) ◽

pp. 988-998 ◽

Cited By ~ 9

Author(s):

Lei Zheng ◽

Jingxuan Pan

Keyword(s):

Uveal Melanoma ◽

Artemisia Annua ◽

Antimalarial Activity ◽

Annexin V ◽

Soft Agar ◽

Melanoma Cells ◽

Luciferase Reporter ◽

Cancer Drug ◽

Migration And Invasion

Background: Uveal melanoma is the most common primary intraocular malignancy in adults. So far, there have been no effective targeted therapeutic agents in patients with uveal melanoma. Artesunate is a semi-synthetic derivative of artemisinin extracted from traditional Chinese medicine Artemisia annua L for treatment of severe and multidrug-resistant malaria. Besides its antimalarial activity, artesunate is identified as an anti-cancer drug due to the inhibition of Wnt/β- catenin pathway in multiple types of cancer. However, the effect of artesunate on uveal melanoma remains unknown. Objective: We evaluated the anti-tumor effects of artesunate on uveal melanoma cells, and analyzed in terms of Wnt/β-catenin pathway, cell growth, cell death, cell migration, invasion and cancer stemlike cells (CSCs) properties. Methods: Primary (92.1, Mel270) and metastatic (Omm1 and Omm2.3) uveal melanoma cells were used. Immunofluorescence staining, dual luciferase reporter assay, Western blotting, MTS, soft agar cloning technique, Annexin V/PI analyses, wound healing scratch assay, in vitro transwell migration and invasion assays, aldehyde dehydrogenase (ALDH) analyses and melanosphere formation assay et al. were carried out. Results: Artesunate suppressed the phosphorylation of GSK3β at S9, and lowered the protein level of β-catenin and its downstream targets (c-Myc, cyclin D1). Artesunate potently inhibited cell viability and colony formation ability. Treatment with artesunate significantly induced apoptosis. In addition, artesunate significantly reduced the migration and invasion of uveal melanoma cells, impaired the traits of CSCs in vitro. Conclusion: Artesunate may be a potential interest for the therapy of uveal melanoma.

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