{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:59:43Z","timestamp":1792789183122,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Children\u2019s Medical Center","award":["SCMC-XEQ-202603"],"award-info":[{"award-number":["SCMC-XEQ-202603"]}],"id":[{"id":"https:\/\/ror.org\/00cd9s024","id-type":"ROR","asserted-by":"crossref"}]},{"award":["SCMC-XEQ-202603"],"award-info":[{"award-number":["SCMC-XEQ-202603"]}],"id":[{"id":"https:\/\/ror.org\/00cd9s024","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Clinical Research Plan of SHDC","award":["SHDC22025306"],"award-info":[{"award-number":["SHDC22025306"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Giant congenital melanocytic nevus (GCMN) is a rare developmental disorder arising from abnormal proliferation and differentiation of neural crest\u2013derived melanocytes. It poses substantial clinical challenges due to cosmetic disfigurement, malignant potential, and the limited efficacy of current treatments. This study aimed to investigate the therapeutic effects and underlying molecular mechanisms of tunlametinib (HL-085), a novel selective MEK1\/2 inhibitor, in GCMN. Methods: Primary GCMN cells and human GCMN explants were isolated, cultured, and validated to establish in vitro cellular and explant models. Following tunlametinib treatment, global transcriptional changes were analyzed using bulk RNA sequencing. Melanogenesis was assessed via Fontana\u2013Masson staining, Western blotting, and immunofluorescence. Cell viability, apoptosis, and cell cycle distribution were evaluated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blotting for apoptosis- and cell cycle\u2013related proteins. Results: Tunlametinib treatment significantly suppressed melanogenesis in GCMN cells and explant tissues at the phenotypic, histological, and protein levels, and reduced cell viability in a concentration-dependent manner. Transcriptomic analysis revealed marked alterations in gene expression profiles following treatment, with prominent changes in apoptosis- and cell cycle\u2013related genes. Subsequent cellular assays and tissue staining confirmed that tunlametinib significantly increased early apoptosis and induced G1\/S cell cycle arrest. Conclusions: Collectively, our findings demonstrate that tunlametinib inhibits proliferation and melanin production in GCMN cells by modulating the RAS-ERK pathway, providing a theoretical basis for its use as a targeted therapeutic strategy for GCMN.<\/jats:p>","DOI":"10.3390\/cancers18193166","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:19:08Z","timestamp":1790842748000},"page":"3166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tunlametinib Suppresses Melanogenesis Induces Cell Cycle Arrest and Apoptosis in Giant Congenital Melanocytic Nevus Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Jin-Ye","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Dermatology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Wen-Shang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Jia-Long","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"given":"Zhi-Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4661-3035","authenticated-orcid":false,"given":"Lina","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Dan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1038\/jid.2013.70","article-title":"Multiple Congenital Melanocytic Nevi and Neurocutaneous Melanosis Are Caused by Postzygotic Mutations in Codon 61 of NRAS","volume":"133","author":"Kinsler","year":"2013","journal-title":"J. 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