{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:34:27Z","timestamp":1793417667781,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100017957","name":"Health Commission of Guizhou Province","doi-asserted-by":"publisher","award":["gzwkj2024\u2010042"],"award-info":[{"award-number":["gzwkj2024\u2010042"]}],"id":[{"id":"10.13039\/100017957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cisplatin resistance remains a major clinical obstacle in the treatment of tongue squamous cell carcinoma (TSCC). Solute carrier family 7 member 2 (SLC7A2) is a key cationic amino acid transporter, yet its functional significance in TSCC drug resistance has not been explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established cisplatin\u2010resistant TSCC cell lines and performed integrated proteomics and metabolomics. SLC7A2 function was assessed via gain\u2010of\u2010function and loss\u2010of\u2010function assays combined with CCK\u20108, Transwell, wound healing, flow cytometry, Western blot, and RT\u2010qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SLC7A2 was markedly downregulated in both TSCC tissues and cisplatin\u2010resistant cells. Multi\u2010omics analysis revealed significant perturbations in purine metabolism, identifying 6\u2010mercaptopurine (6\u2010MP) as a critical metabolite. SLC7A2 overexpression or combined Cis+6\u2010MP treatment synergistically suppressed proliferation, migration, and invasion while promoting apoptosis. Mechanistically, SLC7A2 expression correlated with p53 signaling activity: SLC7A2 knockdown increased MDM2 expression and induced cisplatin resistance, while SLC7A2 overexpression or Cis+6\u2010MP treatment reversed these effects. Pharmacological inhibition of p53 with PFT\u2010\u03b1 sensitized cells to cisplatin, whereas p53 activation with Nutlin\u20103a partially reversed resistance in a p53\u2010dependent manner.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies SLC7A2 as a regulator of cisplatin response in TSCC, acting through the p53 signaling network. It also highlights 6\u2010MP as a sensitizer, offering a combination strategy to overcome chemoresistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70401","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:17:15Z","timestamp":1784175435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Purine Metabolism With 6\u2010Mercaptopurine Overcomes Solute Carrier Family 7 Member 2 Deficiency\u2010Induced Cisplatin Resistance in Tongue Squamous Cell Carcinoma"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6005-136X","authenticated-orcid":false,"given":"Yu\u2010lu","family":"Mao","sequence":"first","affiliation":[{"name":"GuiZhou University Medical College  Guiyang Guizhou Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben\u2010yuan","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Guiyang Stomatological Hospital  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2404-8128","authenticated-orcid":false,"given":"Yu\u2010long","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Guiyang Stomatological Hospital  Guiyang China"},{"name":"College of Stomatology Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Guiyang Stomatological Hospital  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Guiyang Stomatological Hospital  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010chao","family":"Feng","sequence":"additional","affiliation":[{"name":"GuiZhou University Medical College  Guiyang Guizhou Province China"},{"name":"Department of Oral and Maxillofacial Surgery Guiyang Stomatological Hospital  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000004167"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2025.10.004"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012328"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2764"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.MCT\u201024\u20100306"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010024\u201001026\u20104"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010024\u201006599\u20105"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201002172\u2010y"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010024\u201003038\u20102"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.957983"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368\u2010024\u201000343\u20107"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26093941"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.01.015"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.278166"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12957\u2010025\u201003883\u20102"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010024\u201001527\u20108"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201061951\u20103"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010025\u201006707\u20109"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2025.103026"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2025.120073"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.108693"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.14309\/crj.0000000000001713"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204528"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2025.1701001"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010026\u201001793\u2010x"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103433"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukaryotGeneExpr"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000549"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn115330\u201020240806\u201000463"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112137\u201020241015\u201002336"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/kjm2.70069"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003853\u2010y"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006061\u20100"},{"issue":"11","key":"e_1_2_12_36_1","first-page":"3514","article-title":"EFNB2 Acts as the Target of miR\u2010557 to Facilitate Cell Proliferation, Migration and Invasion in Pancreatic Ductal Adenocarcinoma by Bioinformatics Analysis and Verification","volume":"10","author":"Zhang Y.","year":"2018","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616\u2010022\u201000556\u2010w"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11626\u2010026\u201001183\u2010x"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1085700"}],"container-title":["Oral Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/odi.70401","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/odi.70401","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/odi.70401","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:17:18Z","timestamp":1784175438000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/odi.70401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":38,"alternative-id":["10.1111\/odi.70401"],"URL":"https:\/\/doi.org\/10.1111\/odi.70401","archive":["Portico"],"relation":{},"ISSN":["1354-523X","1601-0825"],"issn-type":[{"value":"1354-523X","type":"print"},{"value":"1601-0825","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"assertion":[{"value":"2026-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"odi.70401"}}