Cutaneous melanocytes and melanoma cells express several opsins, of which melanopsin (OPN4) detects temperature and UVA radiation. To evaluate the interaction between OPN4 and UVA radiation, normal and malignant Opn4^WT and Opn4^KO melanocytes were exposed to three daily low doses (total 13.2 kJ/m²) of UVA radiation. UVA radiation led to a reduction of proliferation in both Opn4^WT cell lines; however, only in melanoma cells this effect was associated with increased cell death by apoptosis. Daily UVA stimuli induced persistent pigment darkening (PPD) in both Opn4^WT cell lines. Upon Opn4 knockout, all UVA-induced effects were lost in three independent clones of Opn4^KO melanocytes and melanoma cells. Per1 bioluminescence was reduced after 1st and 2^nd UVA radiations in Opn4^WT cells. In Opn4^KO melanocytes and melanoma cells, an acute increase of Per1 expression was seen immediately after each stimulus. We also found that OPN4 expression is downregulated in human melanoma compared to normal skin, and it decreases with disease progression. Interestingly, metastatic melanomas with low expression of OPN4 present increased expression of BMAL1 and longer overall survival. Collectively, our findings reinforce the functionality of the photosensitive system of melanocytes that may subsidize advancements in the understanding of skin related diseases, including cancer.

皮肤黑素细胞和黑色素瘤细胞表达多种视蛋白，其中黑视蛋白 (OPN4) 可检测温度和 UVA 辐射。为了评估 OPN4 和 UVA 辐射之间的相互作用，将正常和恶性Opn4 ^WT和Opn4 ^KO黑素细胞暴露于每日 3 次低剂量（总计 13.2 kJ/m ² ）的 UVA 辐射。 UVA 辐射导致两种Opn4 ^WT细胞系增殖减少；然而，仅在黑色素瘤细胞中，这种效应与细胞凋亡导致的细胞死亡增加有关。每日 UVA 刺激可诱导两种Opn4 ^WT细胞系持续色素变黑 (PPD)。 Opn4敲除后， Opn4 ^KO黑色素细胞和黑色素瘤细胞的三个独立克隆中所有 UVA 诱导的作用均消失。 Opn4 ^WT细胞中第一次和第二^次UVA 辐射后Per1生物发光减弱。在Opn4 ^KO黑色素细胞和黑色素瘤细胞中，每次刺激后立即观察到Per1表达急剧增加。我们还发现，与正常皮肤相比， OPN4表达在人类黑色素瘤中下调，并且随着疾病进展而降低。有趣的是， OPN4低表达的转移性黑色素瘤表现出BMAL1表达增加和更长的总生存期。 总的来说，我们的研究结果增强了黑素细胞光敏系统的功能，这可能有助于对包括癌症在内的皮肤相关疾病的理解的进步。