{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:11:41Z","timestamp":1790079101140,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study sought to investigate the impact of MAPK12 on immune evasion in hepatocellular carcinoma (HCC) by modulating PD\u2010L1 expression through the PI3K\/AKT\/mTOR pathway. Using GEPIA, Kaplan\u2013Meier plotter, and TIMER databases, MAPK12 expression in HCC and its prognostic value were analyzed. MAPK12 expression was knocked down in HCC cells using shRNAs, and cell proliferation, migration, invasion, and EMT were evaluated. CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells were co\u2010cultured with HCC cells. An orthotopic HCC mouse model was established to observe tumor growth, survival duration, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration, and levels of cytokines and effector molecules. MAPK12 expression was higher in HCC tissues and cell lines. HCC patients with high MAPK12 exhibited shorter overall survival. MAPK12 knockdown reduced HCC cell growth and EMT progression, suppressed PD\u2010L1 expression, and enhanced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell killing activity. MAPK12 deficiency suppressed the PI3K\/Akt\/mTOR pathway activation, while the PI3K activator (740Y\u2010P) reversed PD\u2010L1 downregulation and immune killing effects. The immunosuppressive effect mediated by MAPK12 overexpression was blocked by the PI3K inhibitor LY294002. MAPK12 knockdown restricted tumor growth and extended survival in mice, accompanied by increased CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration. In summary, MAPK12 promotes HCC immune escape by upregulating PD\u2010L1 via the PI3K\/Akt\/mTOR pathway.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70985","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T16:26:11Z","timestamp":1782750371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MAPK12 Upregulates PD\u2010L1 Expression in Hepatocellular Carcinoma to Induce Immune Suppression Through the PI3K\/AKT\/mTOR Pathway"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2936-0696","authenticated-orcid":false,"given":"Qian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Affiliated Bozhou Hospital of Anhui Medical University Bozhou City Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical The Affiliated Bozhou Hospital of Anhui Medical University Bozhou City Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010hai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The Affiliated Bozhou Hospital of Anhui Medical University Bozhou City Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Liver and Gall Surgical The Affiliated Bozhou Hospital of Anhui Medical University Bozhou City Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01200-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-023-10084-4"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.01.007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1070961"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-023-00535-z"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1133308"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.63537"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2022.13565"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00065"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03529-x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/sci\/9071464"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.819128"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03416-5"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.11.015"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1595463"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70295"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.77619"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.21873\/cgp.20552"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2114851119"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12093"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-0633"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01111-8"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297924120058"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.08.024"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-024-03515-3"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6241"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02023-w"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0870"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032652"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.24920\/21804"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031848"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1112-8"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70985","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70985","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70985","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:44:29Z","timestamp":1790077469000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":32,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/jbt.70985"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70985","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"assertion":[{"value":"2025-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70985"}}