{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:34:14Z","timestamp":1782974054225,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060488"],"award-info":[{"award-number":["82060488"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004763","name":"Natural Science Foundation of Inner Mongolia","doi-asserted-by":"publisher","award":["2023MS08039"],"award-info":[{"award-number":["2023MS08039"]}],"id":[{"id":"10.13039\/501100004763","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteosarcoma (OS) is a highly aggressive mesenchymal bone tumor with a dismal prognosis, and its underlying molecular mechanisms remain elusive. Ribosomal protein L13a (RPL13a) contributes to tumorigenesis, while methyltransferase\u2010like 14 (METTL14), a core m\n                    <jats:sup>6<\/jats:sup>\n                    A methyltransferase, modulates OS progression via epigenetic regulation. Our prior work identified the PTEN\/PI3K\/AKT pathway as a key OS regulator. This study aimed to clarify the regulatory interplay among METTL14, RPL13a and PTEN\/PI3K\/AKT in OS, and verify that METTL14 mediates RPL13a m\n                    <jats:sup>6<\/jats:sup>\n                    A modification to regulate PTEN\/PI3K\/AKT signaling, affecting OS cell proliferation, apoptosis, migration and invasion. METTL14, RPL13a and m\n                    <jats:sup>6<\/jats:sup>\n                    A levels were detected in OS cell lines (U2OS, HOS, MG\u201063) and normal osteoblast hFOB1.19 cells. RPL13a knockdown, PTEN overexpression and METTL14 overexpression models were established in U2OS\/HOS cells. M\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010RIP\u2010qPCR and MeRIP assays confirmed RPL13a m\n                    <jats:sup>6<\/jats:sup>\n                    A modification, with functional (CCK\u20108, flow cytometry, wound healing, Transwell) and molecular (RT\u2010qPCR, Western blotting) assays performed in triplicate replicates. METTL14 and RPL13a were upregulated in U2OS\/HOS cells versus hFOB1.19 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). METTL14 overexpression elevated RPL13a m\n                    <jats:sup>6<\/jats:sup>\n                    A modification by ~1.8\u2010fold (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05); si\u2010RPL13a reduced RPL13a mRNA by &gt;\u200960% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). RPL13a knockdown promoted apoptosis, inhibited proliferation\/migration\/invasion, downregulated PTEN and activated PI3K\/AKT signaling, partially reversed by PTEN overexpression. METTL14 overexpression upregulated RPL13a\/PTEN and suppressed PI3K\/AKT activation, abolished by RPL13a knockdown. METTL14 appears to mediate the m6A methylation modification of RPL13a mRNA. Downregulation of RPL13a is associated with reduced PTEN and activated PTEN\/PI3K\/AKT signaling, which may ultimately contribute to suppressed osteosarcoma cell proliferation, migration, and invasion while promoting apoptosis.\n                  <\/jats:p>","DOI":"10.1002\/jor.70232","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:21:31Z","timestamp":1780399291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["METTL14\u2010Mediated RPL13A Expression Regulates Apoptosis and Invasion of Osteosarcoma via the PTEN\/PI3K\/AKT Signaling Pathway"],"prefix":"10.1002","volume":"44","author":[{"given":"Zilong","family":"Chen","sequence":"first","affiliation":[{"name":"Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqi","family":"Pan","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Wei","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxiang","family":"Tong","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaguang","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozhong","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xue","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Meng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3089-2598","authenticated-orcid":false,"given":"Wei","family":"Feng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Inner Mongolia Medical University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040976"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.11.027"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15713"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101728"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-023-00246-z"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00803-9"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02105-9"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115496"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.10.014"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.32725\/jab.2020.008"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009039"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2018.02.013"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI88069"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01500-4"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-022-02214-z"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S284273"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100973"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2025.124081"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.109964"},{"key":"e_1_2_12_21_1","first-page":"217194","article-title":"METTL3\u2010mediated 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