{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:08:06Z","timestamp":1789524486408,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20211026"],"award-info":[{"award-number":["BK20211026"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>A number of studies have demonstrated that N6\u2010methyladenosine (m6A) plays a vital role in the pathological process of various tumours. Recently, it was found that m6A writers or erasers affect the tumourigenesis of melanoma. However, the relationship between m6A readers such as YTH domain family (YTHDF) proteins and melanoma was still elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RT\u2010qPCR, Western blot and immunohistochemistry were conducted to measure the expression level of YTH N6\u2013methyladenosine RNA binding protein 3 (YTHDF3) and lysyl oxidase\u2013like 3 (LOXL3) in melanoma tissues and cells. The effects of YTHDF3 and LOXL3 on melanoma were verified in vitro and in vivo. Multi\u2010omics analysis including RNA\u2010seq, MeRIP\u2010seq, RIP\u2010seq and mass spectrometry analyses was performed to identify the target. The interaction between YTHDF3 and LOXL3 was verified by RT\u2010PCR, Western blot, MeRIP\u2010qPCR, RIP\u2010qPCR and CRISPR\u2010Cas13b\u2010based epitranscriptome engineering.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, we found that m6A reader YTHDF3 could affect the metastasis of melanoma both in vitro and in vivo. The downstream targets of YTHDF3, such as LOXL3, phosphodiesterase 3A (PDE3A) and chromodomain helicase DNA\u2010binding\u00a0protein\u00a07\u00a0(CHD7) were identified by means of RNA\u2010seq, MeRIP\u2010seq, RIP\u2010seq and mass spectrometry analyses. Besides, RT\u2010qPCR, Western blot, RIP\u2010qPCR and MeRIP\u2010qPCR were performed for subsequent validation. Among various targets of YTHDF3, LOXL3 was found to be the optimal target of YTHDF3. With the application of CRISPR\u2013Cas13b\u2010based epitranscriptome engineering, we further confirmed that the transcript of LOXL3 was captured and regulated by YTHDF3 via m6A binding sites. YTHDF3 augmented the protein expression of LOXL3 without affecting its mRNA level via the enrichment of eukaryotic translation initiation factor 3 subunit A (eIF3A) on the transcript of LOXL3. LOXL3 downregulation inhibited the metastatic ability of melanoma cells, and overexpression of LOXL3 ameliorated the inhibition of melanoma metastasis caused by YTHDF3 downregulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The YTHDF3\u2010LOXL3 axis could serve as a promising target to be interfered with to inhibit the metastasis of melanoma.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1075","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T05:23:56Z","timestamp":1667453036000},"source":"Crossref","is-referenced-by-count":37,"title":["N6\u2010methyladenosine reader YTHDF3 regulates melanoma metastasis via its \u2018executor' LOXL3"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6718-9675","authenticated-orcid":false,"given":"Hao\u2010ze","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Pathology, Institute of Dermatology Chinese Academy of Medical 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