[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-330317-105":59,"doc-detail-330317-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","nnt-as1-in-cafs-derived-exosomes-promotes-progression-and-glucose-metabolism-through-mir-889-3phif-1-in-pancreatic-adenocarcinoma","NNT-AS1 inCAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma","","Pancreatic adenocarcinoma exhibits poor survival and aggressive behavior driven by metabolic reprogramming and tumor microenvironment signaling. This work investigates how cancer-associated fibroblasts (CAFs) communicate with tumor cells via CAF-derived exosomes, focusing on the lncRNA NNT-AS1. Exosomal NNT-AS1 is shown to modulate glucose metabolism, proliferation, and metastasis in PDAC cells. Mechanistically, NNT-AS1 functions as a molecular sponge for miR-889-3p, thereby regulating HIF-1α and glycolytic remodeling, identifying potential therapeutic targets for PDAC.",{"@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/nnt-as1-in-cafs-derived-exosomes-promotes-progression-and-glucose-metabolism-through-mir-889-3phif-1-in-pancreatic-adenocarcinoma/330317/",{"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/nnt-as1-in-cafs-derived-exosomes-promotes-progression-and-glucose-metabolism-through-mir-889-3phif-1-in-pancreatic-adenocarcinoma/330317.png","ImageObject",300,407,{"name":92,"@type":93},"Lucas Martin","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What biological pathway does the study focus on in PDAC?","Question",{"text":112,"@type":113},"The study focuses on an exosomal axis involving lncRNA NNT-AS1, miR-889-3p, and HIF-1α, linking CAF-derived signaling to glycolytic remodeling in PDAC cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How are CAF-derived exosomes assessed in the experiments?",{"text":117,"@type":113},"Transmission electron microscopy is used to examine exosomes secreted by patient-derived CAFs, followed by molecular assays such as qRT-PCR and binding validation with dual luciferase reporter assays.",{"name":119,"@type":110,"acceptedAnswer":120},"What effects do CAF-derived exosomal NNT-AS1 have on PDAC cells?",{"text":121,"@type":113},"CAF-derived exosomal NNT-AS1 alters glucose metabolism, promotes proliferation, and increases metastasis in PDAC cells after co-culture.","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},330317,1790487793,{"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":39,"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":145,"preview_page_count":4},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nNNT‑AS1 inCAFs‑derived exosomes promotes progression and glucose metabolism through miR‑889‑3p/HIF‑1α in pancreatic adenocarcinoma  \nPingping Zhang1, Qun Wang2, Weijun Lu2, Feng Zhang2, Dongde Wu2 & Junwei Sun2*  \nIt is metabolic and signaling crosstalk between stromal cells and tumors in the tumor microenvironment, which influences several aspects of tumor formation and drug resistance, including metabolic reprogramming. Despite considerable findings linking lncRNAs in HIF‑1‑related regulatory networks to cancer cell, little emphasis has been given to the role in communication between cancer‑associated fibroblasts (CAFs) and tumor cells. Previously, we observed that NNT‑AS1 was substantially expressed in CAFs cells and CAFs exosomes, and subsequently investigated the influence of CAFs exosomal NNT‑AS1 on glucose metabolism, proliferation, and metastasis of pancreatic ductaladenocarcinoma (PDAC) cells. Transmission electron microscopy was used to examine exosomes secreted by PDAC patient‑derived CAFs. qRT‑PCR was used to evaluate the expression of NNT‑AS1, miR‑889‑3p, and HIF‑1. The role of CAFs‑derived exosomal NNT‑AS1 in PDAC cell progression and metabolism have been identified. Dual luciferase reporter assays examined the binding between NNT‑AS1, miR‑889‑3p, and HIF‑1. After PDAC cells co‑culture exosomes secreted by CAFs, we found that they alter glucose metabolism, proliferation, and metastasis. In PDAC cells, CAF‑derived exosomal lncRNA NNT‑AS1 acted as a molecular sponge for miR‑889‑3p. Furthermore, HIF‑1 could be targeted by miR‑889‑3p and was controlled by NNT‑AS1. This study explores the mechanism by which NNT‑AS1 influences the interaction of CAFs on glycolytic remodeling, proliferation, and metastasis of tumor cells through regulating miR‑889‑3p/HIF‑1α, which also helps discover new clinical treatment targets for PDAC.  \nKeywords CAFs-derived exosomes, NNT-AS1, PDAC, miR-889-3p, HIF-1α, Glucose metabolism  \nAbbreviations  \nNNT-AS1 PDAC  \nCAFs  \nNF  \nFAP  \nTMELncRNACCK-8 HIF-1 LDHA  \nPKM2  \nSDH  \nFH  \nNicotinamide nucleotide transhydrogenase-antisense RNA1 Pancreatic ductal adenocarcinoma  \nCancer-associated fibroblasts Normal fibroblasts Fibroblast activating protein Tumor microenvironment Long noncoding RNA  \nCell counting kit-8  \nHypoxia inducible factor 1  \nLactate dehydrogenase AM2-type pyruvate kinase Succinate dehydrogenase Fumarate hydratase  \n1Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2Department of Hepatic & Biliary & Pancreatic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. *email: [junweisunHBCH@hotmail.com](junweisunHBCH@hotmail.com)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nOD Optical density  \nSD Standard deviation  \nPancreatic ductal adenocarcinoma is one of the most aggressive gastrointestinal malignancies, with a 5-year survival rate of less than 10%1. Metabolic reprogramming, often known as the Warburg effect, is one of cancer’sten hallmarks. It is important for cancer growth, including invasion and metastasis. Changes in the microenvironment can activate and maintain HIF, which, in turn, stimulates the transcription of related genes involved in metabolic reprogramming and PDAC generation, invasion, metastasis, and angiogenesis2,3. Meanwhile, cancerassociated fibroblasts (CAFs), a kind of activated fibroblast, are present in practically all solid tumors, especially in pancreatic, breast, and prostate cancers4–6. CAFs play a critical role in the formation and progression of a variety of cancers since they are one of the most important components of the tumor microenvironment (TME) . Tumor cells and CAFs communicate in a variety of ways. It has been found that CAFs can aid cancer cells in acquiring energy, synthetic pro","cbCaigmWPTxg12ZY","https://ap.wps.com/l/cbCaigmWPTxg12ZY","pdf",7769188,11,"English","# Background\n## Tumor metabolic reprogramming and HIF signaling\n## Role of CAFs and tumor microenvironment\n## Exosomes and long noncoding RNAs\n# Study rationale and prior findings\n## NNT-AS1 and cancer progression\n## miR-889-3p and signaling context\n# Methods overview\n## Exosome isolation and identification\n## Gene expression analysis and interaction validation\n# Mechanistic framework\n## NNT-AS1/miR-889-3p/HIF-1α axis\n## Effects on glycolysis, proliferation, and metastasis","[{\"question\":\"What biological pathway does the study focus on in PDAC?\",\"answer\":\"The study focuses on an exosomal axis involving lncRNA NNT-AS1, miR-889-3p, and HIF-1α, linking CAF-derived signaling to glycolytic remodeling in PDAC cells.\"},{\"question\":\"How are CAF-derived exosomes assessed in the experiments?\",\"answer\":\"Transmission electron microscopy is used to examine exosomes secreted by patient-derived CAFs, followed by molecular assays such as qRT-PCR and binding validation with dual luciferase reporter assays.\"},{\"question\":\"What effects do CAF-derived exosomal NNT-AS1 have on PDAC cells?\",\"answer\":\"CAF-derived exosomal NNT-AS1 alters glucose metabolism, promotes proliferation, and increases metastasis in PDAC cells after co-culture.\"}]","NNT-AS1 inCAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma | PDF",1789988130,28]