[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-352511-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-352511-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","snrpd2-mediated-regulation-of-ddx39b-splicing-promotes-endometrial-cancer-progression-by-suppressing-the-activation-of-ctsc-cryptic-exons","SNRPD2-mediated regulation of DDX39B splicing promotes endometrial cancer progression by suppressing the activation of CTSC cryptic exons","","Sm proteins are overexpressed across cancers, but the specific Sm family member driving endometrial cancer and its mechanism remain unclear. This study shows SNRPD2 is markedly upregulated in endometrial cancer specimens and correlates with worse clinical outcomes. SNRPD2 silencing suppresses proliferation and metastasis in vitro and in vivo, including via ASOs reducing tumor growth in a PDX model. Mechanistically, SNRPD2 prevents intron retention in DDX39B, thereby limiting cryptic exon activation and CTSC downregulation that supports malignant phenotypes.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/snrpd2-mediated-regulation-of-ddx39b-splicing-promotes-endometrial-cancer-progression-by-suppressing-the-activation-of-ctsc-cryptic-exons/352511/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/snrpd2-mediated-regulation-of-ddx39b-splicing-promotes-endometrial-cancer-progression-by-suppressing-the-activation-of-ctsc-cryptic-exons/352511.png","ImageObject",300,407,{"name":42,"@type":43},"River Wang","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":26},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What role does SNRPD2 play in endometrial cancer progression?","Question",{"text":62,"@type":63},"SNRPD2 is markedly upregulated in endometrial cancer specimens, and its higher expression correlates with poorer clinical outcomes. Functional experiments show that silencing SNRPD2 suppresses proliferation and metastasis.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How do antisense oligonucleotides (ASOs) targeting SNRPD2 affect tumors?",{"text":67,"@type":63},"ASOs targeting SNRPD2 markedly reduce tumor growth in a patient-derived xenograft (PDX) model, supporting SNRPD2 as a potential therapeutic target.",{"name":69,"@type":60,"acceptedAnswer":70},"What mechanism links SNRPD2 to altered splicing of DDX39B and CTSC?",{"text":71,"@type":63},"SNRPD2 knockdown induces retention of intron 5 in DDX39B, producing a noncoding transcript degraded via nonsense-mediated decay (NMD). Reduced DDX39B permits activation of a cryptic exon (Exon 2_3) in CTSC mRNA, introducing premature termination codons and triggering additional NMD-mediated degradation, decreasing CTSC expression.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},352511,1790192886,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":26,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nSNRPD2-mediated regulation of DDX39B splicing promotes endometrial cancer progression by suppressing the activation of CTSC cryptic exons  \nYingwei Li 1,5 ✉, Zhongshao Chen2,5, Yanling Liu3, Yuehan Gao2, Yingying Pu2, Qianqian Gao2, Feng Gao4, Ning Yang2 and Peng Li2  \n© The Author(s) 2026  \n\n|  |  |  |\n| --- | --- | --- |\n|  | Recent studies have reported the overexpression of Sm proteins in several cancers, suggesting their potential as therapeutic targets; however, the specific Sm family members involved in endometrial cancer and their mechanisms remain unclear. Here, we show that the Sm protein SNRPD2 is markedly upregulated in both fresh-frozen and formalin-fixed paraffin-embedded (FFPE) endometrial cancer specimens and that its overexpression correlates with poorer clinical outcomes. In vitro and in vivo functional assays demonstrate that silencing SNRPD2 suppresses endometrial cancer cell proliferation and metastasis. Specifically, antisense oligonucleotides (ASOs) targeting SNRPD2 markedly reduced tumor growth in a patient-derived xenograft (PDX) model. Mechanistic analyses reveal that SNRPD2 knockdown induces the retention of intron 5 in DDX39B, resulting in the production of anoncoding transcript that is degraded by the nonsense-mediated decay (NMD) pathway and thereby decreases DDX39B expression. Reduced DDX39B levels permit the activation of a cryptic exon (Exon 2_ 3) in the CTSC mRNA, which introduces premature termination codons (PTCs) and triggers additional NMD-mediated degradation, leading to decreased CTSC expression. Thus, SNRPD2 maintains high DDX39B expression by preventing intron retention, and in turn, elevated DDX39B expression suppresses cryptic exon usage in CTSC to preserve CTSC expression, ultimately supporting malignant phenotypes of endometrial cancer. These results define a novel SNRPD2–DDX39B–CTSC regulatory axis and identify SNRPD2 as a promising therapeutic target |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  | for endometrial cancer. |  |\n|  | Cell Death and Disease (2026)17:239; [https://doi.org/10.1038/s41419-026-08489-4](https://doi.org/10.1038/s41419-026-08489-4) |  |\n|  |  |  |\n\nINTRODUCTION  \nEndometrial cancer is among the leading malignancies of the female reproductive system and is the most common gynecologic cancer in Western countries [1] . Its incidence is increasing, driven in part by increasing rates of obesity, longer life expectancy, and lower fertility [2] . Although early-stage endometrial cancer generally has a favorable prognosis (5-year survival of approximately 95%), the outlook for advanced cases is poor (5-year survival of only ~19%) [3] . The American Cancer Society estimates that 69,120 new endometrial cancer cases and 13,860 deaths will occur in 2025 [4], with a projected 40–50% increase in incidence by 2030, accompanied by a continuous increase in mortality [5, 6] . In China, the incidence and mortality are likewise increasing, with 81,964 new cases and 16,607 deaths reported in 2020, representing a substantial share of the global burden [7] . At present, the primary treatment modalities for endometrial cancer include hysterectomy, radiotherapy, chemotherapy, endocrine therapy and immunotherapy; however, endocrine approaches have limited efficacy, and hysterectomy is incompatible with preserving  \nfertility [8] . These limitations highlight the need to identify new molecular targets and therapeutic strategies.  \nPre‑mRNA splicing is a fundamental step in gene expression that removes introns and ligates exons to produce mature mRNAs [9] . Alternative splicing, which affects nearly all multi‑exon genes, increases proteomic diversity and regulates many cellular programs [10] . Splicing is performed by the spliceosome, a dynamic complex composed of five small nuclear ribonucleoproteins (snRNPs: U1, U2, U4, U5 a","cbCaiqT6Mbvo7i6C","https://ap.wps.com/l/cbCaiqT6Mbvo7i6C","pdf",18011664,17,"English","# Introduction\n## Endometrial cancer burden and current therapies\n## Pre-mRNA splicing and Sm protein ring formation\n## Dysregulated splicing in cancer\n# Main findings (article abstract)","[{\"question\":\"What role does SNRPD2 play in endometrial cancer progression?\",\"answer\":\"SNRPD2 is markedly upregulated in endometrial cancer specimens, and its higher expression correlates with poorer clinical outcomes. Functional experiments show that silencing SNRPD2 suppresses proliferation and metastasis.\"},{\"question\":\"How do antisense oligonucleotides (ASOs) targeting SNRPD2 affect tumors?\",\"answer\":\"ASOs targeting SNRPD2 markedly reduce tumor growth in a patient-derived xenograft (PDX) model, supporting SNRPD2 as a potential therapeutic target.\"},{\"question\":\"What mechanism links SNRPD2 to altered splicing of DDX39B and CTSC?\",\"answer\":\"SNRPD2 knockdown induces retention of intron 5 in DDX39B, producing a noncoding transcript degraded via nonsense-mediated decay (NMD). Reduced DDX39B permits activation of a cryptic exon (Exon 2_3) in CTSC mRNA, introducing premature termination codons and triggering additional NMD-mediated degradation, decreasing CTSC expression.\"}]","SNRPD2-mediated regulation of DDX39B splicing promotes endometrial cancer progression by suppressing the activation of CTSC cryptic exons | PDF",1790100059,43]