{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T04:20:03Z","timestamp":1783830003065,"version":"3.55.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Jiangsu Province High-level Health Talents \u201cSix Ones Project\u201d Top-notch Talent Project","award":["LGY2020063"],"award-info":[{"award-number":["LGY2020063"]}]},{"name":"2021 Zhenjiang City \u201cJinshan Talent\u201d High-level Leading Talent Training Plan","award":["2021-169DT-20"],"award-info":[{"award-number":["2021-169DT-20"]}]},{"name":"2024 Zhenjiang City Science and Technology Innovation Fund"},{"name":"Key R&D Plan\u2014Social Development","award":["SH2024050"],"award-info":[{"award-number":["SH2024050"]}]},{"name":"Beijing Bethune Charitable Foundation","award":["2024-YJ-156-J-072"],"award-info":[{"award-number":["2024-YJ-156-J-072"]}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Neurotensin receptor 1 (NTSR1) is a high-affinity receptor for neurotensin. Its abnormal expression correlates with cancer development. However, its mechanisms in promoting the malignant progression and irinotecan resistance in lung adenocarcinoma (LUAD) remain unelucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NTSR1 expression in LUAD and its relationship with patients\u2019 prognosis were analyzed by bioinformatics analysis. NTSR1 expression in a human normal pulmonary epithelial cell line and LUAD cell lines was detected by RT-qPCR and Western blot. Cell proliferation ability was examined using the CCK-8 assay and colony formation assay. Flow cytometry was employed to detect cell cycle and apoptosis. The Transwell assay was undertaken to assess cell migration and invasion ability. DNA damage was detected using the comet assay and \u03b3-H2AX immunofluorescence. Dot-blot and methylated RNA immunoprecipitation\u2013qPCR were employed to examine m6A methylation levels. The interaction between IGF2 mRNA binding protein (IGF2BP3) and NTSR1 was verified by RNA immunoprecipitation and dual luciferase experiments. Immunohistochemistry was applied to analyze protein expression in mouse tumor tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>NTSR1 was upregulated in LUAD cells, affecting patients\u2019 dismal overall survival. NTSR1 knockdown hindered cell proliferation, migration, and invasion, and reinforced apoptosis and irinotecan sensitivity. Mechanistically, IGF2BP3 interacted with NTSR1 and induced m6A methylation modification to enhance transcriptional stability, advancing the malignant progression of LUAD and irinotecan resistance. Additionally, NTSR1 knockdown enhanced the sensitivity of LUAD to irinotecan in mice and induced DNA damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, IGF2BP3-mediated NTSR1 m6A methylation expedites LUAD malignant progression and reinforces irinotecan resistance. Targeting this pathway may be an effective method for treating LUAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1165\/rcmb.2024-0487oc","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T19:00:40Z","timestamp":1758654040000},"page":"364-374","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":1,"title":["IGF2BP3-mediated NTSR1 m6A methylation enhances irinotecan resistance and lung adenocarcinoma malignant progression"],"prefix":"10.1093","volume":"74","author":[{"given":"Hao","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Respiratory Disease, Affiliated People\u2019s Hospital of Jiangsu University , Zhenjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease, Affiliated People\u2019s Hospital of Jiangsu University , 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