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RNA-seq results show downregulation of ion channels AQP1, AQP4, and CLIC5 alongside upregulation of membrane lipid metabolism enzymes, including phosphatidylcholine, sphingomyelin, cholesterol, and reduced cardiolipin. These lipid and ion channel shifts suggest impaired oxygen permeability, mitochondrial dysfunction, hypoxia, and reactive oxygen species generation, with HIF1α and ROS-responsive transcriptional and epigenetic regulators elevated in tumors.",{"@graph":69,"@context":122},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/aqp14-clic5-dysregulation-and-lipid-metabolism-alterations-in-lung-cancer/350494/",{"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/aqp14-clic5-dysregulation-and-lipid-metabolism-alterations-in-lung-cancer/350494.png","ImageObject",300,407,{"name":92,"@type":93},"Jasmine","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Which datasets were used to study lung cancer–associated dysregulation?","Question",{"text":112,"@type":113},"RNA-seq was generated from paired tumors and adjacent normal tissues from nine patients with LUSC and LUAD. Additional analyses used RNA-seq data from TCGA, including paired tumor/normal samples and tumor-only samples.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What ion channels and lipid metabolism enzymes changed in lung tumors?",{"text":117,"@type":113},"AQP1, AQP4, and CLIC5 were significantly downregulated in tumors. Enzymes involved in membrane lipid metabolism, including phosphatidylcholine, sphingomyelin, and cholesterol, were upregulated, while cardiolipin was downregulated.",{"name":119,"@type":110,"acceptedAnswer":120},"How do the authors link these molecular changes to tumor microenvironment biology?",{"text":121,"@type":113},"The study suggests impaired oxygen permeability and mitochondrial function, which promotes hypoxia and reactive oxygen species (ROS) production. This is accompanied by elevated hypoxia-related genes and ROS-responsive transcription factors, including Uhrf1 overexpression in tumors.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},350494,1790198614,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},2336478487870,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","BMB Reports  \nBMB Rep. 2026; 59(6): 329-340  \n[www.bmbreports.org](www.bmbreports.org)  \nAQP1/4, CLIC5 dysregulation and lipid metabolism alterationsin lung cancer  \nHeung-Seok Bae1,2 & Je-Yoel Cho1,2, *  \n1Department of Biochemistry, College of Veterinary Medicine, Research Institute for Veterinary Science, BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul 08826, 2Comparative Medicine Disease Research Center (CDRC), Science Research Center (SRC), Seoul National University, Seoul 08826, Korea  \nTo advance the development of novel therapies for lung cancer, we investigated tumor-associated molecules implicated in tumorigenesis. RNA-seq data were generated from paired tumors and adjacent normal tissues of four patients with lung squamous cell carcinoma (LUSC) and five patients with lung adenocarcinoma (LUAD). Additional analyses utilized RNA-seq data from The Cancer Genome Atlas (TCGA), including paired tumor and adjacent normal samples (51 LUSC, 57 LUAD) and tumor-only samples (450 LUSC, 461 LUAD). Adjacent normal tissues served as controls. Our RNA-seq results showed strong concordance with TCGA data. Ion channels Aqp1, Aqp4, and Clic5 were significantly downregulated in lung tumors, whereas enzymes involved in membrane lipid metabolism, including phosphatidylcholine (PC), sphingomyelin (SM), and cholesterol (Cho), were upregulated in lung tumors. Cardiolipin (CL), a mitochondrial inner membrane lipid, was downregulated in lung tumors. These changes might have impaired oxygen permeability and mitochondrial function, promoting hypoxia and reactive oxygen species (ROS) production. Hif1􀁄 expression was elevated in both LUSCand LUAD, along with a hypoxia-responsive protein kinase Csnk2a1 and its downstream targets Hdac1 and Hdac2. ROS-responsive transcription factors Yy1, Foxm1, E2f1, and E2f8 were also significantly upregulated in both LUSC and LUAD. Notably, the master epigenetic regulator Uhrf1 activated by these transcription factors showed marked overexpression in tumors compared to that in normal tissues. TCGA data corroborated these findings. Our study identified tumor cell membrane-associated molecules, including ion channels (Aqp1, Aqp4, Clic5) and membrane lipid metabolism enzymes (PC, SM, Cho, and CL), as critical contributors to lung tumorigenesis. These molecules represent promising targets for developing innovative anti-cancer therapies.[BMB Reports 2026; 59(6): 329-340]  \n*Corresponding author. Tel: +82-2-880-1268; Fax: +82-2-886- 1268; [E-mail: jeycho@snu.ac.kr](E-mail: jeycho@snu.ac.kr)  \n[https://doi.org/10.5483/BMBRep.2024-0160](https://doi.org/10.5483/BMBRep.2024-0160)  \nReceived 14 October 2024, Revised 13 November 2024, Accepted 12 February 2025, Published online 30 June 2026  \nKeywords: Aqp1/4, Cholesterol, Clic5, Hypoxia, ROS  \nINTRODUCTION  \nLung cancer can be categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) . It remains the leading cause of cancer-related deaths worldwide (1-3) . Early detection and identifying cancer biomarkers and drug targets are crucial for improving diagnostic and therapeutic outcomes. Established lung cancer biomarkers include CYFRA21-1, CEA, SCC, NSE, ProGRP, and EGFR (4) . In NSCLC, mutations in proto-oncogenes and tumor suppressor genes such as EGFR (69.5%), TP53 (56.6%), ERBB2 (9.8%), CDKN2A (7.8%), and KRAS (7.0%) have been identified as potential or established drug targets (5) .  \nGoing beyond current anticancer drugs that focus on blocking cell division, to understand and access the state of cells, we investigated tumorigenesis-associated molecules in NSCLC. The cell membrane is critical to maintaining cellular homeostasis and mediating responses to external stimuli, with ion channels and lipids being key components (6-9) . Ion channels convert external chemical and physical signals into electrical signals, especially in excitable tissues such as nerves and muscles. Dysfunctions i","cbCaiqogsm4ukdb6","https://ap.wps.com/l/cbCaiqogsm4ukdb6","pdf",1760151,12,"English","# Introduction\n## Lung cancer background and biomarker needs\n## Rationale for focusing on membrane ion channels and lipids\n## RNA-seq approach and key findings","[{\"question\":\"Which datasets were used to study lung cancer–associated dysregulation?\",\"answer\":\"RNA-seq was generated from paired tumors and adjacent normal tissues from nine patients with LUSC and LUAD. Additional analyses used RNA-seq data from TCGA, including paired tumor/normal samples and tumor-only samples.\"},{\"question\":\"What ion channels and lipid metabolism enzymes changed in lung tumors?\",\"answer\":\"AQP1, AQP4, and CLIC5 were significantly downregulated in tumors. Enzymes involved in membrane lipid metabolism, including phosphatidylcholine, sphingomyelin, and cholesterol, were upregulated, while cardiolipin was downregulated.\"},{\"question\":\"How do the authors link these molecular changes to tumor microenvironment biology?\",\"answer\":\"The study suggests impaired oxygen permeability and mitochondrial function, which promotes hypoxia and reactive oxygen species (ROS) production. This is accompanied by elevated hypoxia-related genes and ROS-responsive transcription factors, including Uhrf1 overexpression in tumors.\"}]","AQP1/4, CLIC5 Dysregulation and Lipid Metabolism Alterations in Lung Cancer | PDF",1790089295]