[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-380703-105":59,"doc-detail-380703-en":129},{"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":122,"head_meta":124,"extra_data":126,"updated_unix":128},105,"en","gata6-as1-suppresses-epithelialmesenchymal-transition-of-pancreatic-cancer-under-hypoxia-through-regulating-snai1-mrna-stability","GATA6-AS1 suppresses epithelial–mesenchymal transition of pancreatic cancer under hypoxia through regulating SNAI1 mRNA stability","","Pancreatic ductal adenocarcinoma (PDAC) develops within a hypoxic microenvironment, shows marked heterogeneity, and frequently recurs. This study identifies a pronounced decrease of the long non-coding RNA GATA6-AS1 in PDAC from GEO data and patient cohorts, where low GATA6-AS1 associates with worse clinicopathologic features and poorer prognosis. Functional experiments show GATA6-AS1 suppresses proliferation, invasion, migration, and EMT under hypoxia, and in vivo data support reduced tumor growth and lung metastasis. Mechanistically, hypoxia-driven ETS1 downregulates GATA6-AS1, which elevates FTO and stabilizes SNAI1 mRNA via m6A-dependent regulation.",{"@graph":69,"@context":121},[70,84,104],{"@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/gata6-as1-suppresses-epithelialmesenchymal-transition-of-pancreatic-cancer-under-hypoxia-through-regulating-snai1-mrna-stability/380703/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/gata6-as1-suppresses-epithelialmesenchymal-transition-of-pancreatic-cancer-under-hypoxia-through-regulating-snai1-mrna-stability/380703.png","ImageObject",300,407,{"name":92,"@type":93},"Blitz","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What relationship links GATA6-AS1 expression with PDAC outcomes?","Question",{"text":111,"@type":112},"GATA6-AS1 expression is significantly decreased in PDAC, and low levels correlate with unfavorable clinicopathologic characteristics and poor prognosis.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How does GATA6-AS1 affect PDAC cell behavior under hypoxia?",{"text":116,"@type":112},"GATA6-AS1 suppresses PDAC proliferation, invasion, migration, and the epithelial–mesenchymal transition (EMT) process under hypoxic conditions.",{"name":118,"@type":109,"acceptedAnswer":119},"What mechanism connects hypoxia, ETS1, GATA6-AS1, FTO, and SNAI1?",{"text":120,"@type":112},"Hypoxia-driven ETS1 is required for the downregulation of GATA6-AS1. GATA6-AS1 inhibits FTO expression and represses SNAI1 mRNA stability in an m6A-dependent manner.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},380703,1790270068,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":138,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":139,"faqs":140,"seo_title":141,"seo_description":67,"update_tm":142,"read_time":143},24464137899374,"https://us-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Zhou et al. Journal of Translational Medicine (2023) 21:882  \n[https://doi.org/10.1186/s12967-023-04757-5](https://doi.org/10.1186/s12967-023-04757-5)  \nJournal of Translational Medicine  \n RESEARCH Open Access  \nGATA6-AS1  \nsuppresses epithelial–  \nmesenchymal transition of pancreatic cancer under hypoxia through regulating SNAI1 mRNA stability  \nYunhui Zhou1†, Xinyi Zhou1†, Qiwen Ben2†, Ningning Liu1, Jiahui Wang1, Yongpeng Zhai1, Yichen Bao 1 and Lin Zhou1*  \nAbstract  \nPancreatic ductal adenocarcinoma (PDAC) is characterized by a hypoxic microenvironment, a high rate of heterogeneity as well as a high likelihood of recurrence. Mounting evidence has affirmed that long non-coding RNAs (lncRNAs) participate in the carcinogenesis of PDAC cells. In this study, we revealed significantly decreased expression of GATA6-AS1 in PDAC based on the GEO dataset and our cohorts, and showed that low GATA6-AS1 expression was linked to unfavorable clinicopathologic characteristics as well as a poor prognosis. Gain-and loss-of-function studies demonstrated that GATA6-AS1 suppressed the proliferation, invasion, migration, and epithelial–mesenchymal transition (EMT) process of PDAC cells under hypoxia. In vivo data confirm the suppressive roles of GATA6-AS1/SNAI1 in tumor growth and lung metastasis of PDAC. Mechanistically, hypoxia-driven E26 transformation-specific sequence-1 (ETS1), as an upstream modulatory mechanism, was essential for the downregulation of GATA6-AS1 in PDAC cells. GATA6-AS1 inhibited the expression offat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) eraser, and repressed SNAI1 mRNA stability in an m6A-dependent manner. Our data suggested that GATA6-AS1 can inhibit PDAC cell proliferation, invasion, migration, EMT process and metastasis under hypoxia, and disrupting the GATA6-AS1/FTO/SNAI1 axis might be a viable therapeutic approach for refractory hypoxic pancreatic cancers.  \nKeywords Hypoxia, GATA6-AS1, N6-Methyladenosine, Epithelial–mesenchymal transition, Pancreatic ductaladenocarcinoma  \n†Yunhui Zhou, Xinyi Zhou and Qiwen Ben contributed equally to this work.  \n*Correspondence: Lin Zhou [ZL372@aliyun.com](ZL372@aliyun.com)  \n1 Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou 450052, China  \n2 Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China  \nIntroduction  \nHypoxia is a prevalent feature among solid tumors and facilitates the progression of several malignancies [1]. Pancreatic ductal adenocarcinoma (PDAC) is among the most prevalent fatal solid tumors in both sexes in the US, with a 5-year relative survival of 8% or lower [2, 3]. Increasing evidence affirms that hypoxia has a central function in stimulating the epithelial–mesenchymal transition (EMT), which is fundamental for PDAC invasion, metastasis, and therapy resistance [4, 5]. A core set of EMT-activating transcription factors (EMT‐TFs) are involved in the execution of the EMT program and these  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/","cbCaimgItZfHj2Pv","https://ap.wps.com/l/cbCaimgItZfHj2Pv","pdf",10161268,"English","# Abstract\n## Keywords\n## Introduction","[{\"question\":\"What relationship links GATA6-AS1 expression with PDAC outcomes?\",\"answer\":\"GATA6-AS1 expression is significantly decreased in PDAC, and low levels correlate with unfavorable clinicopathologic characteristics and poor prognosis.\"},{\"question\":\"How does GATA6-AS1 affect PDAC cell behavior under hypoxia?\",\"answer\":\"GATA6-AS1 suppresses PDAC proliferation, invasion, migration, and the epithelial–mesenchymal transition (EMT) process under hypoxic conditions.\"},{\"question\":\"What mechanism connects hypoxia, ETS1, GATA6-AS1, FTO, and SNAI1?\",\"answer\":\"Hypoxia-driven ETS1 is required for the downregulation of GATA6-AS1. GATA6-AS1 inhibits FTO expression and represses SNAI1 mRNA stability in an m6A-dependent manner.\"}]","GATA6-AS1 suppresses epithelial–mesenchymal transition of pancreatic cancer under hypoxia through regulating SNAI1 mRNA stability | PDF",1790241384,48]