{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:05:33Z","timestamp":1784099133492,"version":"3.55.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ81069"],"award-info":[{"award-number":["2025JJ81069"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2026JJ80657"],"award-info":[{"award-number":["2026JJ80657"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aristolochic Acid I (AAI) is a potent nephrotoxin and Group 1 carcinogen. Despite stringent regulatory restrictions, AAI-containing herbal remedies are still sporadically used to treat respiratory symptoms, presenting a previously underappreciated exposure risk for patients with lung adenocarcinoma (LUAD). However, the specific tumor-promoting effects of AAI on preexisting LUAD remain to be fully elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we integrated network toxicology, TCGA transcriptomic analysis, and molecular docking to identify core oncogenic networks potentially affected by AAI. The associated pro-tumor phenotypes and transcriptional regulatory abnormalities were subsequently investigated through a series of\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Network analysis and TCGA data mining identified a cluster of seven hub genes\u2014including ERBB2, SERPINE1, CCNA2, and CHEK1\u2014that are crucial to LUAD progression and significantly associated with poor clinical prognosis. Molecular docking simulations suggested potential binding affinities between AAI and these target proteins. Functional assays demonstrated that acute AAI exposure significantly accelerated the proliferation, migration, and invasion of LUAD cell lines (PC9 and NCI-H1299)\n                      <jats:italic>in vitro<\/jats:italic>\n                      , while promoting macroscopic xenograft tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      . The RT-qPCR and WB results showed that AAI exposure was accompanied by an increase in the expression of core genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that, beyond its established chronic mutagenic toxicity, AAI may act as a potent tumor promoter in LUAD. By potentially influencing key oncogenic networks, AAI accelerates the malignant progression of LUAD, underscoring the severe clinical hazards of AAI exposure in patients with preexisting lung malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1860873","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:10:03Z","timestamp":1784095803000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Aristolochic acid I accelerates lung adenocarcinoma progression coupled with the upregulation of core oncogenic networks: an integrated network toxicology and experimental study"],"prefix":"10.3389","volume":"17","author":[{"given":"Linchuan","family":"Mo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Second Xiangya Hospital, Central South University","place":["Changsha, 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