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.

皮肤黑素细胞和黑素瘤细胞表达多种视蛋白，其中黑视蛋白（OPN4）检测温度和UVA辐射。为了评估OPN4和UVA辐射之间的相互作用，将正常和恶性的Opn4 ^WT和Opn4 ^KO黑素细胞暴露于每日三剂量的低剂量UVA辐射（总计13.2 kJ / m ²）。UVA辐射导致两种Opn4 ^WT细胞系的增殖减少。然而，仅在黑色素瘤细胞中，这种作用与凋亡引起的细胞死亡增加有关。每天的UVA刺激会在两种Opn4 ^WT细胞系中诱导持续性色素变黑（PPD）。根据Opn4敲除后，所有UVA诱导的作用在Opn4 ^KO黑色素细胞和黑色素瘤细胞的三个独立克隆中消失。PER1生物发光是第一和2个之后降低^第二在UVA辐射Opn4 ^WT细胞。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，人黑素瘤中的OPN4表达下调，并且随着疾病的进展而降低。有趣的是，低表达OPN4的转移性黑色素瘤会增加BMAL1的表达和更长的整体生存时间。总的来说，我们的发现增强了黑素细胞光敏系统的功能，这可能有助于了解皮肤相关疾病（包括癌症）的进展。