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This study investigates the roles of Metallothionein-1G (MT1G) in GC and its regulatory mechanisms, focusing on iron autophagy. MT1G expression is assessed in Hgc27, MKN45, and AGS cells via RT-qPCR and Western blot, alongside ferroptosis and autophagy marker profiling. Functional effects are evaluated by migration, invasion, mitochondrial potential, Fe2+ and ROS assays. Results show MT1G overexpression suppresses GC cell proliferation and promotes ferroptosis through reduced GPX4/SLC7A11 and inhibits SQSTM1 while activating ARNTL-linked clock autophagy via the GPX4/SQSTM1 axis.",{"@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/mt1g-promotes-iron-autophagy-and-inhibits-the-function-of-gastric-cancer-cell-lines-by-intervening-in-gpx4sqstm1/332780/",{"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/mt1g-promotes-iron-autophagy-and-inhibits-the-function-of-gastric-cancer-cell-lines-by-intervening-in-gpx4sqstm1/332780.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main goal of this study on MT1G in gastric cancer?","Question",{"text":112,"@type":113},"To determine the biological functions of MT1G in gastric cancer cells and clarify the regulatory mechanism underlying iron autophagy and ferroptosis-related changes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does MT1G overexpression affect gastric cancer cell behavior and ferroptosis markers?",{"text":117,"@type":113},"MT1G overexpression inhibits proliferation, migration, and invasion while reducing SOD and GSH, increasing MDA, weakening mitochondrial membrane potential, elevating Fe2+ and ROS, and decreasing GPX4 and SLC7A11 protein expression to promote ferroptosis.",{"name":119,"@type":110,"acceptedAnswer":120},"Which pathway is proposed to connect MT1G, iron autophagy, and clock-related autophagy?",{"text":121,"@type":113},"The study proposes that MT1G acts through the GPX4/SQSTM1 axis to promote ARNTL clock autophagy, with EGLN2 involvement, thereby linking iron autophagy to ARNTL in GC cells.","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},332780,1790251489,{"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":29,"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},962075114765,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nMT1G promotes iron autophagy and inhibits the function of gastric cancer cell lines by intervening in GPX4/SQSTM1  \nKaiqiang Meng4, Jian Song1􀀍, Fan Qi2, Jiamin Li1, Zhichao Fang1 & Liang Song3  \nGastric cancer (GC) is the fifth most common cancer and the third most common cause of cancer death globally, with high invasiveness, high recurrence rate, and poor prognosis. Multiple studies have shown that Metallothionein-1G (MT1G) is closely associated with oxidative stress, ferroptosis, and autophagy. However, the role and potential mechanisms of MT1G in GC have not been fully elucidated. This study aims to explore the biological functions and regulatory mechanisms of MT1G in GC. Perform bioinformatics analysis using theTCGA database to investigate the expression of MT1Gin GC. RT-qPCR and Western blot were used to detect the expression of MT1G, ferroptosis related proteins, autophagy related proteins andARNTL clock autophagy related proteins in Hgc27, MKN45 andAGS cell lines. Exploring the biological functions of MT1G overexpressing GC cell lines through wound healing and transwell experiments. Use specific fluorescence probes to examine mitochondrial membrane potential and Fe2+ fluorescence intensity. Using immunoprecipitation analysis (CO-IP) to elucidate the association between GC cell lines GPX4, SQSTM andARNTL. Use flow cytometry to detect ROS expression. Observation of autophagy related morphological changes in cells using transmission electron microscopy. Compared with gastric mucosal cell lines, the expression of MT1Gis decreased in three gastric cancer cell lines (Hgc27, MKN45 andAGS) . Overexpression of MT1G inhibits the proliferation, migration, and invasion functions of GC cells, reduces SOD and GSH content, increases MDA content, cause the mitochondrial membrane potential to weaken and promote the transformation of JC-1 aggregates to JC-1 monomer, increases Fe2+, affects ROS, and reduces GPX4 and SLC7A11 protein expression, promoting ferroptosis. Overexpression of MT1G promotes the transformation of LC3B Ito LC3B II, reduces SQSTM1 protein expression, and leads to the appearance of more autophagosomes and autolysosomes at low magnification. At high magnification, mitochondrial autophagy, endoplasmic reticulum autophagy, lipid droplet autophagy, and wrinkled mitochondrial cristae are observed, promoting autophagy. Overexpression of MT1G inhibits GPX4, thereby affecting SQSTM1 as a vector to promote ARNTL autophagy and EGLN2, promoting ARNTLclock autophagy through the GPX4/SQSTM1 axis. Our research findings elucidate that overexpression of MT1G promotes iron autophagy centered around ARNTL inGC cells via the GPX4/SQSTM1 axis, thereby inhibiting GC cell function and providing a new molecular mechanism and therapeutic target for the development of GC.  \nKeywords MT1G, Ferroptosis, Autophagy, ARNTL, Clock autophagy, Gastric cancer  \nAbbreviations  \nGC Gastric cancer  \nMT1G Metallothionein-1G  \nGPX4 Phospholipid hydroperoxide glutathione peroxidase SLC7A11 Cystine/glutamate transporter  \n1First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China. 2College of Integrated Traditional Chinese and Western Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China. 3Basic Medical College, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China.  \n4First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China. 􀀍 email: [xuchongling@hhu.edu.cn](xuchongling@hhu.edu.cn)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nFSP1 Ferroptosis suppressor protein 1  \nDHODH Dihydroorotate dehydrogenase (quinone) SQSTM1 Sequestosome-1  \nLC3B Recombinant Human Microtubule-Associated Protein 1 Light Chain 3 Beta  \nARNTL Basic helix-loop-helix ARNT-like protein 1 EGLN2 Egl nine homolog 2  \nRSL3 (1S,3R)-RSL3  \nFer-1 F","cbCaiaQ4GNRtCdfv","https://ap.wps.com/l/cbCaiaQ4GNRtCdfv","pdf",22287779,17,"English","# Introduction\n## Gastric cancer burden and need for new targets\n## Metallothionein-1G and oxidative-stress relevance\n# Materials and Methods\n## Cell models and MT1G expression analysis\n## Functional assays: migration, invasion, and wound healing\n## Ferroptosis and autophagy detection (molecular and imaging)\n# Results\n## MT1G is reduced in gastric cancer cells\n## MT1G overexpression inhibits malignant behaviors and triggers ferroptosis\n## MT1G promotes iron autophagy via GPX4/SQSTM1–ARNTL-related pathways\n# Discussion\n## Proposed molecular mechanism and therapeutic implications","[{\"question\":\"What is the main goal of this study on MT1G in gastric cancer?\",\"answer\":\"To determine the biological functions of MT1G in gastric cancer cells and clarify the regulatory mechanism underlying iron autophagy and ferroptosis-related changes.\"},{\"question\":\"How does MT1G overexpression affect gastric cancer cell behavior and ferroptosis markers?\",\"answer\":\"MT1G overexpression inhibits proliferation, migration, and invasion while reducing SOD and GSH, increasing MDA, weakening mitochondrial membrane potential, elevating Fe2+ and ROS, and decreasing GPX4 and SLC7A11 protein expression to promote ferroptosis.\"},{\"question\":\"Which pathway is proposed to connect MT1G, iron autophagy, and clock-related autophagy?\",\"answer\":\"The study proposes that MT1G acts through the GPX4/SQSTM1 axis to promote ARNTL clock autophagy, with EGLN2 involvement, thereby linking iron autophagy to ARNTL in GC cells.\"}]","MT1G promotes iron autophagy and inhibits the function of gastric cancer cell lines by intervening in GPX4/SQSTM1 | PDF",1789999494,43]