OPN3 Regulates Melanogenesis in Human Congenital Melanocytic Nevus Cells through Functional Interaction with BRAFV600E
OPN3 Regulates Melanogenesis in Human Congenital Melanocytic Nevus Cells through Functional Interaction with BRAFV600E
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DOI：
10.1016/j.jid.2022.04.022
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发表时间：
2022-10-20
影响因子：
6.5
通讯作者：
Lu, Hongguang
中科院分区：
文献类型：
--
作者：
Dong, Xian;Zeng, Wen;Lu, Hongguang
OPN3, as a member of the opsin family, has various nonlight-dependent functions. Congenital melanocytic nevus (CMN) is a skin lesion with dark pigmentation that appears at birth and can be initiated by the BRAF(V600E) mutation in melanocytes. However, the role of OPN3 in BRAF(V600E) CMN cell melanogenesis has never been reported. In this study, we show that OPN3 acts as a negative regulator of melanin production by modulating BRAF(V600E) signaling in BRAF(V600E) CMN cells. Knocking down OPN3 expression can inhibit the BRAF(V600E)/extracellular signal-regulated kinase signaling pathway and upregulate the expression of microcephaly-related transcription factors, tyrosinase, and TRP1 and TRP2, thus increasing melanin levels in BRAF(V600E) CMN cells. More remarkably, OPN3 and BRAF(V600E) were found to form a physical complex. Furthermore, a three-dimensional nevus model was used to further prove the negative regulatory effect of OPN3 on BRAF(V600E) CMN cell melanogenesis. Our study reveals a mechanism for OPN3-mediated melanogenesis in BRAF(V600E) CMN cells, and these results may lead to a more personalized and economically viable approach to treating BRAF(V600E) CMN.
