{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:29:03Z","timestamp":1791919743537,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Malignant melanoma is a leading cause of skin cancer\u2010related death. In over 30% of cases, the melanoma is invasive and has a metastatic phenotype. KCNQ1 overlapping transcript 1 (KCNQ1OT1) was previously identified as an oncogenic long noncoding RNA (lncRNA). Our study intends to uncover the mechanism of KCNQ1OT1 functioning in melanoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>qRT\u2010PCR, immunohistochemical analysis, and Western blotting were used to investigate mechanisms of the lncRNA KCNQ1OT1, on its downstream genes in melanoma tissues, cells as well as the impact on CD8+ T cells. Proliferation, apoptosis, and migration\/invasion were assessed in melanoma cells to evaluate the effects of KCNQ1OT1, miR\u201034a, and signal transducer and activator of transcription 3 (STAT3). The RNA interactions were determined by dual\u2010luciferase reporter, and melanoma cells were co\u2010cultured with CD8+ T cells to study immune evasion. A lactate dehydrogenase (LDH) cytotoxicity assay was used to investigate the cytotoxicity of CD8+ T cells toward melanoma cells. The in vivo tumorigenic potential of KCNQ1OT1 was defined using xenograft models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>KCNQ1OT1 was upregulated in melanoma tissues leading to a poor prognosis, and knocking down it inhibited melanoma cell proliferation, migration, and invasion. KCNQ1OT1 regulated the progression of the melanoma via its action as a miR\u201034a sponge. STAT3 was found to be a downstream target of miR\u201034a, resulting in transcriptional regulation of Programmed cell death 1 ligand 1 (PD\u2010L1). KCNQ1OT1 regulated STAT3 by targeting miR\u201034a. Knockdown of KCNQ1OT1 reduced PD\u2010L1 level, enhanced CD8+ T cell cytotoxicity, and proliferation and inhibited apoptosis of CD8+ T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Melanoma cells overexpressed KCNQ1OT1, which influenced the miR\u201034a\/STAT3 axis, to promote proliferation, migration, and invasion of melanoma cells. In addition, KCNQ1OT1 inhibited CD8+ T cell function, also via the miR\u201034a\/STAT3\/PD\u2010L1 axis, thus promoting immune evasion of melanoma cells. The current findings expose a potential therapeutic target of melanoma.<\/jats:p><\/jats:sec>","DOI":"10.1002\/tox.23687","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T18:26:45Z","timestamp":1668796005000},"page":"368-380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<scp>KCNQ1OT1<\/scp> sponges <scp>miR<\/scp>\u201034a to promote malignant progression of malignant melanoma via upregulation of the <scp>STAT3<\/scp>\/<scp>PD\u2010L1<\/scp> axis"],"prefix":"10.1002","volume":"38","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery The First Affiliated Hospital of Anhui Medical University  Hefei Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Department of General Surgery The First Affiliated Hospital of Anhui Medical University  Hefei Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Department of General Surgery The First Affiliated Hospital of Anhui Medical University  Hefei Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery The First Affiliated Hospital of Anhui Medical University  Hefei Anhui People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hainian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery The First Affiliated Hospital of Anhui Medical University  Hefei Anhui People's Republic of 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