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They are one of the key factors in the occurrence, development and metastasis of melanoma. This study demonstrates that <jats:italic>MLLT3<\/jats:italic> is a transcription factor that regulates the stemness and progression of melanoma. <jats:italic>MLLT3<\/jats:italic> interacted with <jats:italic>HMGB1<\/jats:italic> to inhibit its entry into the nucleus, <jats:italic>MLLT3<\/jats:italic> interacted with <jats:italic>YBX1<\/jats:italic> to inhibit its reading of m<jats:sup>5<\/jats:sup>C of <jats:italic>MAGEA1<\/jats:italic>, thereby inhibiting the mRNA stability of <jats:italic>MAGEA1<\/jats:italic>, and directly transcribed P53 to inhibit the stemness, proliferation and metastasis of melanoma cells. This study further explored the potential mechanism of the interaction between miR\u2010542\u20103p\/miR\u20103922\u20103p and <jats:italic>MLLT3<\/jats:italic>. Furthermore, the scRNA\u2010seq of melanoma cells with <jats:italic>MLLT3<\/jats:italic> knock\u2010out resulted in important changes in cell subsets, activating the TP53 and MAPK pathways and transforming into stem cells. The results indicate that the transcription factor <jats:italic>MLLT3<\/jats:italic> is a suppressor gene that regulates the stemness and progression of melanoma, and is expected to become a target for melanoma therapy.<\/jats:p>","DOI":"10.1002\/advs.202408529","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T04:06:14Z","timestamp":1735013174000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["MLLT3 Regulates Melanoma Stemness and Progression by Inhibiting HMGB1 Nuclear Entry and MAGEA1 M<sup>5<\/sup>C Modification"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9136-4990","authenticated-orcid":false,"given":"Yaling","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Health Engineering Shen Zhen Institutes of Advanced Technology Chinese Academy of Science  Shenzhen Guangdong 518055 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