Melanopsin (Opn4) is an oncogene in cutaneous melanoma

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Identifying novel therapeutic targets for cutaneous melanoma is crucial.
• Opsins, known for light and thermal sensing, were investigated for potential tumor-modulatory roles in melanoma.

Purpose of the Study:

• To evaluate the effect of OPN4 (Opn4) on melanoma cancer progression.
• To determine if opsins could serve as therapeutic targets for melanoma.

Main Methods:

• Experimental evaluation of melanoma cell proliferation and cell cycle progression in the presence and absence of Opn4.
• In vivo tumor progression studies using Opn4 knockout (Opn4^KO) and wild-type (Opn4^WT) cells.
• Pharmacological assays, analysis of The Cancer Genome Atlas (TCGA) database, and proteomic analyses of tumor bulk.

Main Results:

• Melanoma cells lacking Opn4 (Opn4^KO) exhibited slower proliferation, impaired cell cycle progression, and reduced melanocyte inducing transcription factor (Mitf) expression compared to Opn4^WT cells.
• In vivo, Opn4^KO tumors showed reduced progression, enhanced immune system response, and impaired guanylyl cyclase activity.
• TCGA data and proteomic analyses confirmed that reduced MITF and OPN4 expression correlates with slower cell cycle, increased immune cells in the tumor microenvironment (TME), and altered signaling pathways.

Conclusions:

• OPN4 acts as an oncogene in melanoma, promoting tumor growth and immune suppression.
• Targeting OPN4 may offer a novel therapeutic strategy for cutaneous melanoma.
• Opn4 modulation impacts melanoma cell cycle, Mitf signaling, guanylyl cyclase activity, and the tumor immune microenvironment.