{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:27:36Z","timestamp":1786627656784,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"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":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lung cancer remains the leading cause of cancer\u2010related mortality worldwide, largely due to therapeutic resistance and tumor progression. Mitochondrial ribosomal proteins (MRPs), particularly MRPS23, have recently emerged as critical regulators of cancer progression in various malignancies, while N6\u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) modification has been established as a key epigenetic mechanism driving tumorigenesis. However, whether\n                    <jats:italic>MRPS23<\/jats:italic>\n                    is regulated by m\n                    <jats:sup>6<\/jats:sup>\n                    A modification and contributes to lung cancer pathogenesis remains completely unexplored. Here, we identified MRPS23 as a critical oncogenic driver in non\u2010small cell lung cancer (NSCLC).\n                    <jats:italic>MRPS23<\/jats:italic>\n                    expression was significantly upregulated in NSCLC tissues and cell lines, and high MRPS23 levels correlated with poor patient prognosis. Mechanistically, we demonstrated that\n                    <jats:italic>WTAP<\/jats:italic>\n                    \u2010mediated m\n                    <jats:sup>6<\/jats:sup>\n                    A methylation and subsequent\n                    <jats:italic>IGF2BP3<\/jats:italic>\n                    recognition stabilized\n                    <jats:italic>MRPS23<\/jats:italic>\n                    mRNA. Functionally, MRPS23 promoted lung cancer progression both in\u00a0vitro and in\u00a0vivo. Further mechanistic studies revealed that MRPS23 exerted its oncogenic effects through physical interaction with the molecular chaperone HSPA8, and this interaction was functionally associated with activation of the RAS\u2013RAF\u2013MEK\u2013ERK signaling cascade. However, the precise molecular steps linking the MRPS23\u2010HSPA8 complex to ERK phosphorylation remain to be fully defined. Collectively, our findings unveil a previously unrecognized m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010dependent MRPS23\/HSPA8\/ERK regulatory axis in NSCLC progression, highlighting MRPS23 and its associated components as promising prognostic biomarkers and therapeutic targets.\n                  <\/jats:p>","DOI":"10.1111\/cas.70496","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T12:29:31Z","timestamp":1786624171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      m\n                      <sup>6<\/sup>\n                      A\n                    <\/scp>\n                    \u2010Mediated Stabilization of\n                    <scp>MRPS23<\/scp>\n                    Drives\n                    <scp>NSCLC<\/scp>\n                    Progression Via\n                    <scp>HSPA8<\/scp>\n                    and\n                    <scp>ERK<\/scp>\n                    Signaling Modulation"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8778-5424","authenticated-orcid":false,"given":"Sihong","family":"Le","sequence":"first","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitao","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianshen","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Nanchang Key Laboratory of Tumor Gene Diagnosis and Innovative Treatment Research  Nanchang China"},{"name":"Department of Oncology, Gaoxin Branch of The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n2363"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.4065\/83.5.584"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010025\u201001679\u20101"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(24)01029\u20108"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11203200"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010025\u201001061\u20107"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1586137"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010024\u201010216\u20104"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina61010096"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010021\u201001785\u20107"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.115523"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2021.145697"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2024.70.12.9"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205493"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094\u2010023\u201003269\u20104"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010019\u20101109\u20109"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12730"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.76798"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108613"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010021\u201000888\u20108"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010023\u201002246\u20106"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010025\u201002399\u20103"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e36469"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010024\u201002959\u20103"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020\u2010024\u201001018\u2010z"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1279735"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.05.010"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001705\u2010z"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.79493"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2025.167827"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1042\/ebc20170057"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.26448"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201022\u20103169"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E24\u201004\u20100194"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2026.156593"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080849"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102731"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168661"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111450"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.09.005"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010022\u201001500\u20104"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u201000450\u2010x"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.04.004"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155761"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201048597\u20103"}],"container-title":["Cancer 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