[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-383735-105":59,"doc-detail-383735-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","characterization-of-a-rhabdomyosarcoma-reveals-a-critical-role-for-smg7-in-cancer-cell-viability-and-tumor-growth","Characterization of a rhabdomyosarcoma reveals a critical role for SMG7 in cancer cell viability and tumor growth","","Soft-tissue sarcomas are aggressive mesenchymal cancers with poor responses and limited targeted options. The work investigates how the nonsense-mediated mRNA decay (NMD) factor SMG7 contributes to sarcoma survival, focusing on a rhabdomyosarcoma model. Inducible SMG7 knockout in Trp53−/− mice inhibits NMD in RMS cells, elevating NMD targets GADD45b and the tumor suppressor lncRNA GAS5, reducing cell viability and limiting tumor growth. SMG7 loss is not required for homeostasis in mouse embryonic fibroblasts and adult mice, suggesting therapeutic benefit.",{"@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/characterization-of-a-rhabdomyosarcoma-reveals-a-critical-role-for-smg7-in-cancer-cell-viability-and-tumor-growth/383735/",{"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/characterization-of-a-rhabdomyosarcoma-reveals-a-critical-role-for-smg7-in-cancer-cell-viability-and-tumor-growth/383735.png","ImageObject",300,407,{"name":92,"@type":93},"Rhys","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-28","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the study address about SMG7 in rhabdomyosarcoma?","Question",{"text":112,"@type":113},"It tests whether SMG7, a key NMD factor, is required for cancer-cell viability and tumor growth in rhabdomyosarcoma.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does SMG7 knockout affect NMD and its downstream targets?",{"text":117,"@type":113},"SMG7 knockout significantly inhibits NMD in RMS cells and induces NMD targets including GADD45b and the tumor suppressor GAS5.",{"name":119,"@type":110,"acceptedAnswer":120},"Why do the findings suggest SMG7 disruption could be a therapeutic strategy?",{"text":121,"@type":113},"The loss of SMG7 reduces RMS cell viability and inhibits tumor growth in vivo, while SMG7 is dispensable for homeostasis in mouse embryonic fibroblasts and adult mice.","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},383735,1790627138,{"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":14,"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},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nCharacterization  \nof a rhabdomyosarcoma reveals a critical role for SMG7 in cancer cell viability and tumor growth  \nAlexander J. Steiner, Yang Zheng & Yi Tang*  \nSoft-tissue sarcomas (STSs) are a rare and diverse group of mesenchymal cancers plagued with aggression, poor response to systemic therapy, and high rates of recurrence. Although STSs generally have low mutational burdens, the most commonly mutated genes are tumor suppressors, which frequently acquire mutations inducing nonsense-mediated mRNA decay (NMD). This suggests  \nthat STS cells may exploit NMD to suppress these anti-cancer genes. To examine the role that the NMD factor SMG7 plays in STS, we developed an inducible knockout mouse model inthe Trp53−/− background. Here, we isolated a subcutaneous STS and identified it as a rhabdomyosarcoma (RMS). We report that knockout ofSMG7 significantly inhibited NMD in our RMS cells, which led to the induction of NMD targets GADD45b and the tumor suppressor GAS5. The loss of NMD and upregulation of these anti-cancer genes were concomitant with the loss of RMS cell viability and inhibited tumor growth. Importantly, SMG7 was dispensable for homeostasis in our mouse embryonic fibroblasts and adult mice. Overall, our data show that the loss ofSMG7 induces a strong anti-cancer effect both in vitro and in vivo. We present here the first evidence that disrupting SMG7 function maybe tolerable and provide a therapeutic benefit for STS treatment.  \nSoft-tissue sarcomas (STSs) are aggressive cancers that respond poorly to chemotherapy and have few efficacious options for targeted therapy1. STSs are mesenchymal cancers that derive from several different lineages, such as cartilage, adipose, fibrous, vasculature, smooth muscle, and skeletal muscle2. STSs are further categorized by their histology, giving rise to more than 70 histological subtypes3. STSs in the adult population are rare (~ 1%), with the incredible diversity of STS resulting in several subtypes being exceedingly rare. The rarity of STS hampers both the exploration of targeted therapies and guidance for systemic therapies. The treatment of STS is further complicated due to the heterogeneous response to systemic therapies across subtypes, such as in rhabdomyosarcoma (RMS). RMS is a skeletal muscle sarcoma characterized by nuclear staining of the myogenic regulatory factors MyoD1 and/or myogenin4,5. The four main histological subtypes of RMS are embryonal, alveolar, spindle cell/sclerosing, and pleomorphic5. RMS is a main cancer seen in children, with subtypes mostly presenting as embryonal or alveolar RMS6,7. The high incidence of RMS in the paediatric population has allowed the standardization of treatment using a multimodal chemotherapeutic strategy, resulting in a 5-year overall survival (OS) rate of 61%6. Pleomorphic RMS is mainly an adult subtype of RMS that responds poorly to the same paediatric multimodal treatment, resulting in a 5-year OS rate of 30%5,8. The poor response rate of chemotherapeutics seen in pleomorphic RMS is common across STSs, which highlights the need for the discovery of viable therapeutic targets.  \nAs STSs exhibit low somatic mutation burdens, with the most frequently mutated genes being tumor suppressors, it may be beneficial to search for therapy targets in the cancer fitness gene category rather than the driver oncogene category9. Cancer fitness genes are distinct from driver oncogenes as they are dispensable for initial transformation10. These genes are utilized by cancer cells to gain proliferative, survival, stress-response, or metastatic benefits during cancer progression, and they tend to be unnecessary for somatic cells under homeostatic conditions10. Nonsense-mediated mRNA decay (NMD) is a pathway that consists of numerous factors, some of which may fall into the cancer fitness gene category11, 12.  \nNMD is a quality control and transcriptomic regulatory p","cbCaioqjowzDQBAf","https://ap.wps.com/l/cbCaioqjowzDQBAf","pdf",7474536,18,"English","# Introduction\n## NMD pathway and SMG7 role in cancer\n# Methods and experimental model\n## Inducible SMG7 knockout in Trp53−/− background\n# Results\n## SMG7 loss inhibits NMD and anti-cancer gene regulation\n## Impact on RMS cell viability and tumor growth\n# Discussion\n## Therapeutic implications and tolerability","[{\"question\":\"What question does the study address about SMG7 in rhabdomyosarcoma?\",\"answer\":\"It tests whether SMG7, a key NMD factor, is required for cancer-cell viability and tumor growth in rhabdomyosarcoma.\"},{\"question\":\"How does SMG7 knockout affect NMD and its downstream targets?\",\"answer\":\"SMG7 knockout significantly inhibits NMD in RMS cells and induces NMD targets including GADD45b and the tumor suppressor GAS5.\"},{\"question\":\"Why do the findings suggest SMG7 disruption could be a therapeutic strategy?\",\"answer\":\"The loss of SMG7 reduces RMS cell viability and inhibits tumor growth in vivo, while SMG7 is dispensable for homeostasis in mouse embryonic fibroblasts and adult mice.\"}]","Characterization of a rhabdomyosarcoma reveals a critical role for SMG7 in cancer cell viability and tumor growth | PDF",1790258949,45]