{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:23:46Z","timestamp":1787027026476,"version":"build-2736575974"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772916, 82103470, 81872216"],"award-info":[{"award-number":["81772916, 82103470, 81872216"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20171132"],"award-info":[{"award-number":["BK20171132"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Although phospholipase A2 group VI (\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    ) is involved in oncogenesis in several human tumors, its expression and role in cutaneous malignant melanoma (CMM) pathogenesis remains unclear. Here, by using the Oncomine and CCLE online database, immunohistochemistry, RT-qPCR, and western blotting analysis, we revealed that\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    was markedly up-regulated in CMM tissues compared to nevus tissues, as well as remarkably increased\n                    <jats:italic>in vitro<\/jats:italic>\n                    in SK-MEL-28 and M14 melanoma cell lines compared to human melanocytes\n                    <jats:italic>. In vivo<\/jats:italic>\n                    ,\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    was also elevated in nine melanoma tissues compared to adjacent tissues. To investigate the malignant behaviors of PLA2G6 in CMM, SK-MEL-28 and M14 cell lines with\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    stable knockdown by RNAi strategy were constructed. Through CCK8 and colony formation assays\n                    <jats:italic>in vitro<\/jats:italic>\n                    and xenograft tumor experiment\n                    <jats:italic>in vivo<\/jats:italic>\n                    , we found that knockdown of\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    dramatically inhibited cell proliferation. The results of scratch-wound and transwell assays suggested that the migration and invasion of melanoma cells were prominently suppressed after silencing\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    . In addition, flow cytometry showed that the knockdown of\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    promoted the apoptosis rate of melanoma cells. To further explore the potential molecular mechanism, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS\/MS) proteomic and bioinformatics analysis. The GO and KEGG analysis suggested that the underlying mechanism of\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    in CMM might be associated with the ferroptosis pathway, and ferroptosis-related proteins were validated to be differentially expressed in\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    knockdown SK-MEL-28 and M14 cells. Together, these results suggested that\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    knockdown significantly inhibited cell proliferation, metastasis, and promoted apoptosis in melanoma. Our findings on the biological function of\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    and the underlying association between\n                    <jats:italic>PLA2G6<\/jats:italic>\n                    and ferroptosis in melanoma may contribute to developing a potential therapeutic strategy for melanoma.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2022.819235","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T08:17:30Z","timestamp":1646641050000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["PLA2G6 Silencing Suppresses Melanoma Progression and Affects Ferroptosis Revealed by Quantitative Proteomics"],"prefix":"10.3389","volume":"12","author":[{"given":"Yifei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuju","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer 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