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Knockdown increases ROS, Fe2+ and lipid peroxidation and promotes ferroptosis through NADPH and FSP1 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was the main question of the research?","Question",{"text":63,"@type":64},"How NADK regulates ferroptosis in lung adenocarcinoma and whether the NADPH/FSP1 axis mediates this effect.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the researchers assess NADK expression and clinical relevance?",{"text":68,"@type":64},"Immunohistochemistry (IHC) measured NADK in 86 LUAD cases and adjacent tissues, followed by statistical comparison for metastasis and five-year survival between high- and low-score groups.",{"name":70,"@type":61,"acceptedAnswer":71},"What happens when NADK is knocked down in LUAD cells?",{"text":72,"@type":64},"NADK knockdown inhibits LUAD cell proliferation and enhances ferroptosis, increasing ROS, Fe2+, and lipid peroxidation products, especially under Erastin/RSL3 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\n[https://doi.org/10.1007/s00432-024-05752-z](https://doi.org/10.1007/s00432-024-05752-z)  \nKnockdown of NADK promotes LUAD ferroptosis via NADPH/FSP1 axis  \nXiangpeng Meng1 · Fang Peng2 · Shijie Yu1 · Xinming Chi1 · Wenchi Wang1 · Shujuan Shao1  \nReceived: 12 March 2024 / Accepted: 18 April 2024 / Published online: 3 May 2024 © The Author(s) 2024  \nAbstract  \nBackground Lung cancer is a serious threat to human health and is the first leading cause of cancer death. Ferroptosis, a newly discovered form of programmed cell death associated with redox homeostasis, is of particular interest in the lung cancer, given the high oxygen environment of lung cancer. NADPH has reducing properties and therefore holds the potential to resist ferroptosis. Resistance to ferroptosis exists in lung cancer, but the role of NADK in regulating ferroptosis in lung cancer has not been reported yet.  \nMethods Immunohistochemistry (IHC) was used to analyse the expression of NADK in 86 cases of lung adenocarcinoma(LUAD) and adjacent tissues, and a IHC score was assigned to each sample. Chi-square and kaplan-meier curve was performed to analyse the differences in metastasis and five-year survival between the two groups with NADK high or low scores. Proliferation of NADK-knockdown LUAD cell lines was detected in vivo and vitro. Furthermore, leves of ROS, MDA and Fe2+ were measured to validate the effect and mechanism of NADK on ferroptosis in LUAD.  \nResults The expression of NADK was significantly evaluated in LUAD tissues as compared to adjacent non-cancerous tissues. The proliferation of NADK-knockdown cells was inhibited both in vivo and vitro, and increasing levels of intracellular ROS, Fe2+ and lipid peroxide products (MDA) were observed. Furthermore, NADK-knockdown promoted the ferroptosisof LUAD cells induced by Erastin/RSL3 by regulating the level of NADPH and the expression of FSP1 . Knockdown of NADK enhanced the sensitivities ofLUAD cells to Erastin/RSL3-induced ferroptosis by regulating NADPH level and FSP1 expression.  \nConclusions NADK is over-expressed in LUAD patients. Knockdown of NADK inhibited the proliferation of LUAD cells both in vitro and in vivo and promotes the Erastin/RSL3-induced ferroptosis ofLUAD cells by down-regulating the NADPH/ FSP1 axis.  \nKeywords Ferroptosis · NADK · NADPH · FSP1 · LUAD  \nIntroduction  \nGlobally, lung cancer ranks second in cancer incidence and continues to lead in cancer mortality. Approximately estimated 1.8 millions people die from lung cancer each year, which is about 2 times the mortality of colorectal cancer, the second leading cause of cancer-related deaths (Sung et al. 2021) . According to the histopathological classification, non-small cell lung cancer (NSCLC) is the most prevalent  \n* Shujuan Shao [shaoshujuan2006@126.com](shaoshujuan2006@126.com)  \n1 Liaoning Key Laboratory of Proteomics, Dalian Medical University, Dalian 116044, China  \n2 Department of Pathologic, The Second Hospital of Dalian Medical University, Dalian 116011, China  \none, accounting for about 85% of lung cancer, of which lungsquamous cell carcinoma, especially lung adenocarcinoma (LUAD) are the two major subtypes of NSCLC (Herbst et al. 2018 ; Molina et al. 2008) . LUAD shows a higher incidence than lung squamous cell carcinoma (Roy-Chowdhuri 2021 ; Ruiz-Cordero and Devine 2020).In non-smoking populations, air pollutants such as PM2.5 are more likely to cause LUAD (Hill et al. 2023) . Therefore, study of the pathogenesis and clinical treatment methods of LUAD is a critical issue that needs to be solved urgently.  \nFerroptosis is a newly identified form of programmed cell death, triggered by an imbalance in cellular redox homeostasis, which is distinct from apoptosis (Cao and Dixon 2016; Dixon et al. 2012 ; Stockwell 2022; Yang and Stockwell 2016) . Ferroptosis has reported to be closely related to various diseases, and resistance to ferroptosis  \nis of great","cbCaisj9mHeG9ptM","https://ap.wps.com/l/cbCaisj9mHeG9ptM","pdf",10885900,13,"English","# Abstract\n# Introduction\n## Ferroptosis and redox control in cancer\n## Ferroptosis resistance in lung cancer\n## Role of NADPH and the NADPH/FSP1 axis","[{\"question\":\"What was the main question of the research?\",\"answer\":\"How NADK regulates ferroptosis in lung adenocarcinoma and whether the NADPH/FSP1 axis mediates this effect.\"},{\"question\":\"How did the researchers assess NADK expression and clinical relevance?\",\"answer\":\"Immunohistochemistry (IHC) measured NADK in 86 LUAD cases and adjacent tissues, followed by statistical comparison for metastasis and five-year survival between high- and low-score groups.\"},{\"question\":\"What happens when NADK is knocked down in LUAD cells?\",\"answer\":\"NADK knockdown inhibits LUAD cell proliferation and enhances ferroptosis, increasing ROS, Fe2+, and lipid peroxidation products, especially under Erastin/RSL3 treatment.\"}]","Knockdown of NADK promotes LUAD ferroptosis via NADPH/FSP1 axis | PDF",1789977614,33]