{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:18:43Z","timestamp":1789593523390,"version":"build-2803163510"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medicine and Health Science Technology Development Plan of Shandong Province","award":["202201050466"],"award-info":[{"award-number":["202201050466"]}]},{"name":"Medicine and Health Science Technology Development Plan of Shandong Province","award":["202312051358"],"award-info":[{"award-number":["202312051358"]}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MH197"],"award-info":[{"award-number":["ZR2022MH197"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"key research and development plan of Jining","award":["2022YXNS152"],"award-info":[{"award-number":["2022YXNS152"]}]},{"name":"key research and development plan of Jining","award":["2023YXNS035"],"award-info":[{"award-number":["2023YXNS035"]}]},{"DOI":"10.13039\/501100010029","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["tsqn202103186"],"award-info":[{"award-number":["tsqn202103186"]}],"id":[{"id":"10.13039\/501100010029","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Gastric cancer (GC) is one of the most common and lethal cancers globally. methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) RNA methylation plays a crucial role in tumor initiation and progression by regulating RNA function. STM2457, a highly efficient METTL3 inhibitor, can inhibit METTL3 activity and may serve as a potential therapeutic strategy in cancers. However, the role of STM2457 for GC cells is still unknown. In this study, we analyzed the expression profile data of GC in TCGA and GEO databases, and further explored the expression involvement of METTL3 in GC cell line, investigated the therapeutic effect of STM2457 targeted inhibition of METTL3 in GC both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiments. The results indicated that STM2457 could suppress GC cell proliferation and migration by inhibiting METTL3, and also promoted cell apoptosis and arrest the cell cycle in S phase. In addition, STM2457 could inhibit tumor growth in subcutaneous xenotransplantation mouse model. Our findings suggested that STM2457 had great potential for the treatment of GC and could serve as a foundation for future clinical applications.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0345744","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:32:08Z","timestamp":1774373528000},"page":"e0345744","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["The METTL3 inhibitor STM2457 suppresses gastric cancer progression by modulating m6A RNA modification"],"prefix":"10.1371","volume":"21","author":[{"given":"Hang","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haozhi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoman","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0493-3281","authenticated-orcid":true,"given":"Kun","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruili","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"issue":"10251","key":"pone.0345744.ref001","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0140-6736(20)31288-5","article-title":"Gastric cancer","volume":"396","author":"EC Smyth","year":"2020","journal-title":"Lancet"},{"issue":"4","key":"pone.0345744.ref002","first-page":"273","article-title":"Molecular pathology of gastric cancer","volume":"22","author":"M Kim","year":"2022","journal-title":"J Gastric Cancer"},{"issue":"18","key":"pone.0345744.ref003","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22189950","article-title":"Molecular landscapes of gastric pre-neoplastic and pre-invasive lesions","volume":"22","author":"G Businello","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"2","key":"pone.0345744.ref004","first-page":"77","article-title":"Survival of metastatic gastric cancer: Significance of age, sex and race\/ethnicity","volume":"2","author":"D Yang","year":"2011","journal-title":"J Gastrointest Oncol"},{"issue":"32","key":"pone.0345744.ref005","doi-asserted-by":"crossref","first-page":"52307","DOI":"10.18632\/oncotarget.10740","article-title":"Metastatic spread in patients with gastric cancer","volume":"7","author":"M Riihim\u00e4ki","year":"2016","journal-title":"Oncotarget"},{"key":"pone.0345744.ref006","doi-asserted-by":"crossref","DOI":"10.12659\/MSM.923867","article-title":"A population-based analysis of distant metastasis in Stage IV Gastric Cancer","volume":"26","author":"Y Zhang","year":"2020","journal-title":"Med Sci Monit"},{"issue":"1","key":"pone.0345744.ref007","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s12943-019-1109-9","article-title":"Functions of N6-methyladenosine and its role in cancer","volume":"18","author":"L He","year":"2019","journal-title":"Mol Cancer"},{"issue":"1","key":"pone.0345744.ref008","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s40364-020-00244-x","article-title":"N6-methyladenine modification in noncoding RNAs and its function in cancer","volume":"8","author":"X Yang","year":"2020","journal-title":"Biomark Res"},{"key":"pone.0345744.ref009","first-page":"670","article-title":"CBX2 and EZH2 cooperatively promote the growth and metastasis of lung adenocarcinoma","volume":"27","author":"F-F Hu","year":"2021","journal-title":"Mol Ther Nucleic Acids"},{"issue":"3","key":"pone.0345744.ref010","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14030560","article-title":"Alternative splicing, epigenetic modifications and cancer: A dangerous triangle, or a hopeful one?","volume":"14","author":"F Gimeno-Valiente","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"2","key":"pone.0345744.ref011","doi-asserted-by":"crossref","first-page":"506","DOI":"10.3390\/ijms19020506","article-title":"Tea polysaccharide prevents colitis-associated carcinogenesis in mice by inhibiting the proliferation and invasion of tumor cells","volume":"19","author":"L-Q Liu","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"5","key":"pone.0345744.ref012","first-page":"1375","article-title":"METTL14 promotes the migration and invasion of breast cancer cells by modulating N6\u2011methyladenosine and hsa\u2011miR\u2011146a\u20115p expression","volume":"43","author":"D Yi","year":"2020","journal-title":"Oncol Rep"},{"key":"pone.0345744.ref013","doi-asserted-by":"crossref","first-page":"641836","DOI":"10.3389\/fcell.2021.641836","article-title":"NUCB1 suppresses growth and shows additive effects with gemcitabine in pancreatic ductal adenocarcinoma via the unfolded protein response","volume":"9","author":"Y-Q Hua","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"pone.0345744.ref014","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.3389\/fonc.2019.01403","article-title":"Multiple functions and mechanisms underlying the role of METTL3 in human cancers","volume":"9","author":"W Zheng","year":"2019","journal-title":"Front Oncol"},{"key":"pone.0345744.ref015","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1146\/annurev-cellbio-100616-060758","article-title":"Rethinking m6A readers, writers, and erasers","volume":"33","author":"KD Meyer","year":"2017","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"2","key":"pone.0345744.ref016","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3892\/or.2021.8114","article-title":"METTL3\u2011mediated m6A modification of Bcl\u20112 mRNA promotes non\u2011small cell lung cancer progression","volume":"46","author":"Y Zhang","year":"2021","journal-title":"Oncol Rep"},{"issue":"7","key":"pone.0345744.ref017","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1136\/gutjnl-2019-319639","article-title":"METTL3-mediated m6A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance","volume":"69","author":"Q Wang","year":"2020","journal-title":"Gut"},{"issue":"6","key":"pone.0345744.ref018","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1002\/hep.29683","article-title":"RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2","volume":"67","author":"M Chen","year":"2018","journal-title":"Hepatology"},{"key":"pone.0345744.ref019","doi-asserted-by":"crossref","DOI":"10.2174\/0118761429322420241112051105","article-title":"Exploring the pharmacological mechanisms of P-hydroxylcinnamaldehyde for Treating Gastric Cancer: A pharmacological perspective with experimental confirmation","volume":"17","author":"S Fatima","year":"2024","journal-title":"Curr Mol Pharmacol"},{"issue":"3","key":"pone.0345744.ref020","doi-asserted-by":"crossref","first-page":"194","DOI":"10.2174\/0109298665350654250111144722","article-title":"Anti-cancer bioactive peptide induces apoptosis in gastric cancer cells through TP53 signaling cascade","volume":"32","author":"Q Suyila","year":"2025","journal-title":"Protein Pept Lett"},{"issue":"2","key":"pone.0345744.ref021","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2174\/0115665232247694230921060213","article-title":"A Retrospective analysis of the lauren classification in the choice of XELOX or SOX as an adjuvant chemotherapy for gastric cancer","volume":"24","author":"K Wang","year":"2024","journal-title":"Curr Gene Ther"},{"issue":"5","key":"pone.0345744.ref022","doi-asserted-by":"crossref","first-page":"390","DOI":"10.2174\/0113892029300608240531111743","article-title":"Crosstalk between cancer-associated fibroblasts and myeloid cells shapes the heterogeneous microenvironment of gastric cancer","volume":"25","author":"Z Peng","year":"2024","journal-title":"Curr Genomics"},{"issue":"7860","key":"pone.0345744.ref023","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41586-021-03536-w","article-title":"Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia","volume":"593","author":"E Yankova","year":"2021","journal-title":"Nature"},{"issue":"6","key":"pone.0345744.ref024","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.jpha.2023.04.009","article-title":"Effects and translatomics characteristics of a small-molecule inhibitor of METTL3 against non-small cell lung cancer","volume":"13","author":"H Xiao","year":"2023","journal-title":"J Pharm Anal"},{"issue":"3","key":"pone.0345744.ref025","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.3892\/ol.2017.5660","article-title":"High BIM mRNA levels are associated with longer survival in advanced gastric cancer","volume":"13","author":"N Wu","year":"2017","journal-title":"Oncol Lett"},{"issue":"2","key":"pone.0345744.ref026","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.tranon.2014.02.014","article-title":"Adjuvant Chemotherapy with Docetaxel, Cisplatin, and Continuous-Infusion 5-Fluorouracil for Gastric Cancer: A Phase II Study","volume":"7","author":"C Meng","year":"2014","journal-title":"Transl Oncol"},{"issue":"3","key":"pone.0345744.ref027","first-page":"2880","article-title":"Corosolic acid reduces 5\u2011FU chemoresistance in human gastric cancer cells by activating AMPK","volume":"18","author":"JB Park","year":"2018","journal-title":"Mol Med Rep"},{"issue":"1","key":"pone.0345744.ref028","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1186\/s12885-022-10136-y","article-title":"Evaluating the efficacy and microenvironment changes of HER2\u2009+\u2009gastric cancer during HLX02 and Endostar treatment using quantitative MRI","volume":"22","author":"J Liang","year":"2022","journal-title":"BMC Cancer"},{"issue":"3","key":"pone.0345744.ref029","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.molcel.2016.03.021","article-title":"The m(6)A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells","volume":"62","author":"S Lin","year":"2016","journal-title":"Mol Cell"},{"issue":"2","key":"pone.0345744.ref030","doi-asserted-by":"crossref","DOI":"10.3390\/biom13020243","article-title":"Critical Roles of METTL3 in translation regulation of cancer","volume":"13","author":"W Meng","year":"2023","journal-title":"Biomolecules"},{"issue":"1","key":"pone.0345744.ref031","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12943-019-1036-9","article-title":"METTL3 promote tumor proliferation of bladder cancer by accelerating pri-miR221\/222 maturation in m6A-dependent manner","volume":"18","author":"J Han","year":"2019","journal-title":"Mol Cancer"},{"issue":"1","key":"pone.0345744.ref032","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13045-020-00895-1","article-title":"Emerging role of RNA methyltransferase METTL3 in gastrointestinal cancer","volume":"13","author":"Q Wang","year":"2020","journal-title":"J Hematol Oncol"},{"issue":"1","key":"pone.0345744.ref033","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12943-019-1038-7","article-title":"METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma","volume":"18","author":"T Li","year":"2019","journal-title":"Mol Cancer"},{"issue":"24","key":"pone.0345744.ref034","doi-asserted-by":"crossref","first-page":"24967","DOI":"10.18632\/aging.103767","article-title":"HBXIP promotes gastric cancer via METTL3-mediated MYC mRNA m6A modification","volume":"12","author":"Z Yang","year":"2020","journal-title":"Aging (Albany NY)"},{"issue":"16","key":"pone.0345744.ref035","doi-asserted-by":"crossref","first-page":"2968","DOI":"10.1038\/s41388-021-01753-1","article-title":"METTL3-mediated m6A methylation of SPHK2 promotes gastric cancer progression by targeting KLF2","volume":"40","author":"F-C Huo","year":"2021","journal-title":"Oncogene"},{"issue":"4","key":"pone.0345744.ref036","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/cac2.12281","article-title":"m6 A-mediated regulation of PBX1-GCH1 axis promotes gastric cancer proliferation and metastasis by elevating tetrahydrobiopterin levels","volume":"42","author":"Y Liu","year":"2022","journal-title":"Cancer Commun (Lond)"},{"key":"pone.0345744.ref037","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3389\/fonc.2020.00115","article-title":"METTL3 Promotes the Progression of Gastric Cancer via Targeting the MYC Pathway","volume":"10","author":"D-D Yang","year":"2020","journal-title":"Front Oncol"},{"issue":"1","key":"pone.0345744.ref038","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12943-022-01522-y","article-title":"Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification","volume":"21","author":"Y Hu","year":"2022","journal-title":"Mol Cancer"},{"issue":"1","key":"pone.0345744.ref039","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12943-022-01521-z","article-title":"METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p\/AKT1S1 axis","volume":"21","author":"H-N Fan","year":"2022","journal-title":"Mol Cancer"},{"issue":"6","key":"pone.0345744.ref040","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41594-021-00606-5","article-title":"Mining for METTL3 inhibitors to suppress cancer","volume":"28","author":"J Li","year":"2021","journal-title":"Nat Struct Mol Biol"},{"issue":"11","key":"pone.0345744.ref041","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1038\/s41388-022-02185-1","article-title":"METTL3 promotes intrahepatic cholangiocarcinoma progression by regulating IFIT2 expression in an m6A-YTHDF2-dependent manner","volume":"41","author":"Q-C Xu","year":"2022","journal-title":"Oncogene"},{"issue":"1","key":"pone.0345744.ref042","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13046-023-02638-9","article-title":"METTL3 promotes chemoresistance in small cell lung cancer by inducing mitophagy","volume":"42","author":"Y Sun","year":"2023","journal-title":"J Exp Clin Cancer Res"},{"issue":"4","key":"pone.0345744.ref043","doi-asserted-by":"crossref","first-page":"111530","DOI":"10.1016\/j.celrep.2022.111530","article-title":"METTL3 regulates m6A methylation of PTCH1 and GLI2 in Sonic hedgehog signaling to promote tumor progression in SHH-medulloblastoma","volume":"41","author":"Z-W Zhang","year":"2022","journal-title":"Cell Rep"},{"issue":"9","key":"pone.0345744.ref044","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/imcb.12581","article-title":"METTL3 inhibition reduces N6 -methyladenosine levels and prevents allogeneic CD4+ T-cell responses","volume":"100","author":"S Li","year":"2022","journal-title":"Immunol Cell Biol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0345744","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:32:14Z","timestamp":1774373534000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0345744"}},"subtitle":[],"editor":[{"given":"Alexander F.","family":"Palazzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0345744","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]}}}