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Long non-coding RNA MNX1-AS1 participates in cancer development, yet its control of regulated cell death remains unclear. MNX1-AS1 knockdown enhances RSL3-driven ferroptosis in NSCLC cells, lowering viability while raising ROS and MDA. MNX1-AS1 depletion also potentiates paclitaxel-induced apoptosis via BAX upregulation and reduced Bcl-2, accompanied by increased cleaved caspase-3 and PARP1. RNA-seq/qRT-PCR implicate ACSL4 in ferroptosis and ABCG2 in apoptosis, and co-treatment with RSL3 plus paclitaxel shows higher sensitivity. These findings suggest MNX1-AS1 as a therapeutic target, particularly with ferroptosis/apoptosis inducers.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/downregulation-of-lncrna-mnx1-as1-promotes-the-ferroptosis-and-apoptosis-of-non-small-cell-lung-cancer/374190/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/downregulation-of-lncrna-mnx1-as1-promotes-the-ferroptosis-and-apoptosis-of-non-small-cell-lung-cancer/374190.png","ImageObject",300,407,{"name":92,"@type":93},"Liam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main finding about MNX1-AS1 in non-small cell lung cancer?","Question",{"text":113,"@type":114},"Knockdown of MNX1-AS1 promotes both RSL3-induced ferroptosis and paclitaxel-induced apoptosis in NSCLC cells.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does MNX1-AS1 knockdown affect ferroptosis-related measurements?",{"text":118,"@type":114},"It increases reactive oxygen species (ROS) and malondialdehyde (MDA) levels and reduces cell viability in the presence of RSL3.",{"name":120,"@type":111,"acceptedAnswer":121},"Which genes are implicated in MNX1-AS1-mediated ferroptosis and apoptosis?",{"text":122,"@type":114},"RNA sequencing and qRT-PCR indicate ACSL4 is increased and ABCG2 is reduced after MNX1-AS1 knockdown; rescue assays suggest ACSL4 and ABCG2 mediate ferroptosis and apoptosis, respectively.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},374190,1790251671,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":41},8796095461564,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Ivyspring  \nInternational Publisher  \nInternationalJournal of Medical Sciences  \n2025; 22(5): 1052-1063. doi: 10.7150/ijms.97790  \nResearch Paper  \nDownregulation of lncRNA MNX1-AS1 promotes the ferroptosis and apoptosis of non-small cell lung cancer  \nXinming Chi1,*, Lingya Feng1,*, Longzhu Wang1,*, Shijie Yu1, Minna Wei1, Qianran Zhang1,2, Xuefeng Liu3,􀀍, Shujuan Shao1,􀀍  \n1. University Key Laboratory of Proteomics in Liaoning Province, Dalian Medical University, Dalian, China.  \n2. Department of Pathology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.  \n3. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.  \n*These authors contributed equally.  \n􀀍 Corresponding authors: Shujuan Shao, University Key Laboratory of Proteomics in Liaoning Province, Dalian Medical University, No.9 West Section Lvshun South Road, Dalian 116044, Liaoning, China. Email: [sjshao@dmu.edu.cn. Xuefeng Liu](sjshao@dmu.edu.cn. Xuefeng Liu), Institute of Cancer Stem Cell, Dalian Medical University, No.9 West Section Lvshun South Road, Dalian 116044, Liaoning, China. Email: [ixuee@sina.com](ixuee@sina.com).  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2024.04.26; Accepted: 2025.01.03; Published: 2025.02.03  \nAbstract  \nNon-small cell lung cancer (NSCLC), the main histological type of lung cancer, poses a serious threat to human health. Increasing evidence has shown that long non-coding RNA (lncRNA) MNX1-AS1 is involved in the development and progression of cancers, including lung cancer. Apoptosis and ferroptosis, which are two forms of regulated cell death, can be induced by anti-cancer drugs. However, the roles of MNX1-AS1 in apoptosis and ferroptosis are still unclear. Here, we found that knockdown of MNX1-AS1 promoted the ferroptosis induced by RSL3 in NSCLC cells, with a decrease in cell viability and increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Meanwhile, acridine orange/ethidium bromide (AO/EB) double staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and Annexin V/PI double staining revealed that knockdown of MNX1-AS1 promoted the apoptosis caused by paclitaxel in NSCLC cells. In addition, knockdown of MNX1-AS1 resulted in increased expression of pro-apoptotic protein BAX as well as the cleaved caspase-3 and PARP1, and decreased expression of anti-apoptotic protein Bcl-2. RNA sequencing and quantitative real-time PCR assay identified that the expression of ACSL4 was increased, while the expression of ABCG2 was reduced when MNX1-AS1 was knocked down. Rescue assay showed that ACSL4 and ABCG2 were involved in MNX1-AS1-mediated ferroptosis and apoptosis, respectively. Furthermore, knockdown of MNX1-AS1 increased the sensitivity of NSCLC cells to the combination of RSL3 and paclitaxel. Taken together, our data suggest that MNX1-AS1 might be a potential therapeutic target for lung cancer, especially in combination of ferroptosis and/or apoptosis-inducing drugs.  \nIntroduction  \nLung cancer remains one of the deadliest human cancers worldwide, which ranks second in incidence and first in mortality, accounting for approximately 11.4% of new cancer cases and 18.0% of cancer deaths in 2020 [1]. Non-small cell lung cancer (NSCLC) is the primary histological subtype of lung cancer, but the treatment options for NSCLC are still limited [2] . Thus, it is urgent to explore new therapeutic targetsand strategies for lung cancer.  \nApoptosis and ferroptosis represent two forms  \nof regulated cell death (RCD) [3] . Ferroptosis is a novel type of RCD driven by iron-dependent lipid peroxidation, which is different from cell apoptosis [4-7] . Although apoptosis and ferroptosi","cbCaiqakm9zzJi4s","https://ap.wps.com/l/cbCaiqakm9zzJi4s","pdf",6802455,12,"English","# Abstract\n## Background\n## Methods and key findings\n## Mechanistic insights\n## Therapeutic implications","[{\"question\":\"What is the main finding about MNX1-AS1 in non-small cell lung cancer?\",\"answer\":\"Knockdown of MNX1-AS1 promotes both RSL3-induced ferroptosis and paclitaxel-induced apoptosis in NSCLC cells.\"},{\"question\":\"How does MNX1-AS1 knockdown affect ferroptosis-related measurements?\",\"answer\":\"It increases reactive oxygen species (ROS) and malondialdehyde (MDA) levels and reduces cell viability in the presence of RSL3.\"},{\"question\":\"Which genes are implicated in MNX1-AS1-mediated ferroptosis and apoptosis?\",\"answer\":\"RNA sequencing and qRT-PCR indicate ACSL4 is increased and ABCG2 is reduced after MNX1-AS1 knockdown; rescue assays suggest ACSL4 and ABCG2 mediate ferroptosis and apoptosis, respectively.\"}]","Downregulation of lncRNA MNX1-AS1 promotes the ferroptosis and apoptosis of non-small cell lung cancer | PDF",1790201273]