[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-372950-105":59,"doc-detail-372950-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","m1a-regulated-diaph3-promotes-the-invasiveness-of-colorectal-cancer-via-stabilization-of-krt19","m1A-regulated DIAPH3 promotes the invasiveness of colorectal cancer via stabilization of KRT19","","m1A-regulated RNA methylation is investigated as a regulatory mechanism in colorectal cancer (CRC) metastasis, focusing on DIAPH3 and its downstream target KRT19. Methylated RNA immunoprecipitation sequencing profiles m1A in tumor and tumor-adjacent tissues from CRC patients. DIAPH3 expression and clinical correlations are assessed via immunohistochemistry and online datasets. Cell migration and invasion are tested with wound healing, Transwell, and xenograft metastasis models, with downstream targets screened by mass spectrometry. DIAPH3-KRT19 signaling drives invasiveness through proteasome-dependent KRT19 stabilization.",{"@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":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/m1a-regulated-diaph3-promotes-the-invasiveness-of-colorectal-cancer-via-stabilization-of-krt19/372950/",{"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/m1a-regulated-diaph3-promotes-the-invasiveness-of-colorectal-cancer-via-stabilization-of-krt19/372950.png","ImageObject",300,407,{"name":92,"@type":93},"Finn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How was the m1A profile in CRC investigated?","Question",{"text":112,"@type":113},"Methylated RNA immunoprecipitation sequencing was performed on tumor tissues and tumor-adjacent normal tissues from CRC patients to determine m1A profiles of mRNA.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role does DIAPH3 play in CRC progression?",{"text":117,"@type":113},"DIAPH3 mRNA and its m1A modifications increase together in CRC tissues, and high DIAPH3 expression correlates with metastasis and progression. DIAPH3 knockdown reduces CRC cell migration and invasion.",{"name":119,"@type":110,"acceptedAnswer":120},"How does KRT19 relate to DIAPH3 function?",{"text":121,"@type":113},"Restoring KRT19 via ectopic plasmid rescues the migration and invasion defects caused by DIAPH3 silencing. A proteasome inhibitor (MG132) blocks DIAPH3-silencing-induced KRT19 degradation, supporting a proteasome-dependent mechanism.","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},372950,1790525642,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"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},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","Clinical & Experimental Metastasis (2025) 42:10 [https://doi.org/10.1007/s10585-024-10323-0](https://doi.org/10.1007/s10585-024-10323-0)  \nm1A‑regulated DIAPH3 promotes the invasiveness of colorectal cancer via stabilization of KRT19  \nShuyi Mi1,2 · Jie Hu1,3 · Wenwen Chen1,2 · Jingyu Chen1,2 · Zhipeng Xu1 · Meng Xue1,2  \nReceived: 12 June 2024 / Accepted: 4 October 2024 / Published online: 22 January 2025 © The Author(s) 2025  \nAbstract  \nBackground In recent years, the emphasis has shifted to understanding the role of N1-methyladenosine (m1A) in tumor progression as little is known about its regulatory effect on mRNA and its role in the metastasis of colorectal cancer (CRC) . Methods We performed methylated RNA immunoprecipitation sequencing of tumor tissues and tumor-adjacent normal tissues from three patients with CRC to determine the m1A profile of mRNA in CRC. The expression of diaphanous-related formin 3 (DIAPH3) and its correlation with clinicopathological characteristics of CRC were evaluated using immunohistochemistry and online datasets. The role of DIAPH3 in the migration and invasion of CRC cells was evaluated using wound healing assay, Transwell assay and xenograft metastatic model. The downstream targets of DIAPH3 were screened using mass spectrometry. By co-transfecting DIAPH3 siRNA and a keratin 19 (KRT19) ectopic plasmid into CRC cells, the role of DIAPH3-KRT19 signaling axis was confirmed.  \nResults The mRNA level of DIAPH3 and its m1A modifications increased simultaneously in the CRC tissues. In addition, high DIAPH3 expression in CRC tissues is significantly associated with metastasis and progression to an advanced stage. After the knockdown of DIAPH3, the migration and invasion capabilities of CRC cells suffered a notable decline, which could be rescued by overexpressing KRT19 . In addition, the proteasome inhibitor MG132 could block the degradation of KRT19 induced by DIAPH3 silencing.  \nConclusions Our study reveals that DIAPH3 mRNA was modified in CRC cells by m1A methylation. Silencing DIAPH3 suppresses the migration and invasion of CRC cells, potentially through the proteasome-dependent degradation of downstream KRT19 .  \nKeywords CRC · m1A · DIAPH3 · Migration · Invasion  \nAbbreviations  \nAJCC American Joint Committee on Cancer  \nCHX Cycloheximide  \nCOAD Colon adenocarcinoma  \nShuyi Mi and Jie Hu have equally contributed to this work.  \n* Zhipeng Xu [2311036@zju.edu.cn](2311036@zju.edu.cn)  \n* Meng Xue [xuemeng@zju.edu.cn](xuemeng@zju.edu.cn)  \n1 Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, No.88, Jiefang Road, Hangzhou 310009, Zhejiang, China  \n2 Institute of Gastroenterology, Zhejiang University, Hangzhou, China  \n3 Department of Gastroenterology, Jiande First People’s Hospital, Jiande, Hangzhou, China  \nCRC  \nDIAPH3  \nGEO  \nGEPIA  \nFBS  \nKO  \nKRT19 IHC  \nLncRNA  \n3-MA  \nm1A  \nm6A  \nMeRIP-seq  \nMFAP2  \nMS  \nREAD  \nColorectal cancer  \nDiaphanous-related formin 3  \nGene Expression Omnibus  \nGene Expression Profiling Interactive  \nAnalysis  \nFetal bovine serum Knockout Keratin 19  \nImmunohistochemistry Long non-coding RNA 3-Methyladenine N1-methyladenosine  \nN6-methyladenosine  \nMethylated RNA immunoprecipitation sequencing  \nMicrofibril associated protein 2  \nMass Spectrometry Rectal adenocarcinoma  \nqPCR Quantitative real-time PCR  \nRIP RNA immunoprecipitation  \nTCGA The Cancer Genome Atlas  \nIntroduction  \nThe significance of genomic, epigenomic, and transcriptomic regulation across the entire cancer life cycle has been extensively studied [1]. Recently, a type of post-transcriptional modifications occurring on RNA molecules called “epitranscriptomics” has gained attention. This includes processes such as RNA editing, slicing and methylation [2]. Among these modifications, RNA methylation, especially N6-methyladenosine (m6A), has been well studied and is considered to play a vital role in the development of various cancers [3]. In recent","cbCaimw2ZEDEtfhX","https://ap.wps.com/l/cbCaimw2ZEDEtfhX","pdf",3546594,15,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n# Materials and methods\n## Clinical CRC samples","[{\"question\":\"How was the m1A profile in CRC investigated?\",\"answer\":\"Methylated RNA immunoprecipitation sequencing was performed on tumor tissues and tumor-adjacent normal tissues from CRC patients to determine m1A profiles of mRNA.\"},{\"question\":\"What role does DIAPH3 play in CRC progression?\",\"answer\":\"DIAPH3 mRNA and its m1A modifications increase together in CRC tissues, and high DIAPH3 expression correlates with metastasis and progression. DIAPH3 knockdown reduces CRC cell migration and invasion.\"},{\"question\":\"How does KRT19 relate to DIAPH3 function?\",\"answer\":\"Restoring KRT19 via ectopic plasmid rescues the migration and invasion defects caused by DIAPH3 silencing. A proteasome inhibitor (MG132) blocks DIAPH3-silencing-induced KRT19 degradation, supporting a proteasome-dependent mechanism.\"}]","m1A-regulated DIAPH3 promotes the invasiveness of colorectal cancer via stabilization of KRT19 | PDF",1790195958,38]