{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T09:11:27Z","timestamp":1772183487100,"version":"3.50.1"},"reference-count":33,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81870033"],"award-info":[{"award-number":["81870033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Foundation for High-level Talents during the 13th Five-year Plan Period of Yangzhou, China","award":["ZDRC201866"],"award-info":[{"award-number":["ZDRC201866"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Recent studies have highlighted the role of ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, in cancer biology. This study aims to investigate the effect of lactotransferrin (LTF) upregulation on the pathological changes related to non-small cell lung cancer (NSCLC)\n                      <jats:italic>via<\/jats:italic>\n                      the inhibition of ferroptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      LTF\u2019s involvement in NSCLC was investigated through cell experiments and clinical samples. Cell models with stable LTF knockdown or overexpression were established by lentiviral transduction. Cell viability and cytotoxicity were evaluated through cell counting kit 8 (CCK8) and lactate dehydrogenase (LDH) experiments. Scratch and Transwell experiments were conducted to verify the effect of LTF expression on the migration and invasion abilities of lung cancer cells. Protein and mRNA expression were analyzed using Western blotting and qPCR. Malondialdehyde (MDA), glutathione (GSH), free iron ions (Fe\n                      <jats:sup>2+<\/jats:sup>\n                      ), and reactive oxygen species (ROS) levels were measured with appropriate kits. The intracellular localization and expression of the protein was detected through immunofluorescence (IF). Peripheral blood of healthy controls and patients with preliminarily diagnosed non-small cell lung cancer was collected, and the expression levels of LTF protein and mRNA were detected by Western blotting and quantitative polymerase chain reaction (qPCR) experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results demonstrate that LTF was upregulated in NSCLC and it\u2019s overexpression could significantly enhance the migration, invasion, and epithelial-mesenchymal transition (EMT) of non-small cell lung cancer cells. The overexpression of LTF significantly inhibited ferroptosis in non-small cell lung cancer cells. LTF modulates the expression of critical regulators of ferroptosis including glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4), leading to altered cellular redox status. The protein and mRNA expression levels of LTF were both increased in the peripheral blood of patients with NSCLC, with changes in protein level being more significant. Additionally, the overexpression of LTF was significantly correlated with the stage of NSCLC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, these findings suggest that LTF upregulation plays a crucial role in inhibiting ferroptosis, thereby influencing the pathological progression of NSCLC. This study provides a potential therapeutic avenue for targeting ferroptosis in NSCLC treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.20866","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T08:34:06Z","timestamp":1772181246000},"page":"e20866","source":"Crossref","is-referenced-by-count":0,"title":["Lactotransferrin upregulation affects the pathological changes of non-small cell lung cancer by regulating 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