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The study shows dsHSATII overexpression drives mesenchymal-like morphology and increases pancreatic cancer cell invasiveness. An RNA-binding protein, STRBP, preferentially binds dsHSATII and rescues mesenchymal transition when overexpressed. Mechanistically, STRBP modulates alternative splicing of EMT-associated genes and produces EMT-like changes via CLSTN1 isoform switching, linking satellite-array dysregulation to tumor progression and poor outcomes.",{"@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/satellite-double-stranded-rna-induces-mesenchymal-transition-in-pancreatic-cancer-by-regulating-alternative-splicing/331933/",{"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/satellite-double-stranded-rna-induces-mesenchymal-transition-in-pancreatic-cancer-by-regulating-alternative-splicing/331933.png","ImageObject",300,407,{"name":92,"@type":93},"Finn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does dsHSATII play in pancreatic cancer cells?","Question",{"text":112,"@type":113},"dsHSATII overexpression promotes mesenchymal-like morphological changes and enhances the invasiveness of pancreatic cancer cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which protein binds dsHSATII and what is its functional effect?",{"text":117,"@type":113},"STRBP preferentially binds dsHSATII RNA, and STRBP overexpression rescues the mesenchymal transition in dsHSATII-expressing cells.",{"name":119,"@type":110,"acceptedAnswer":120},"How does STRBP mechanistically influence EMT-related changes?",{"text":121,"@type":113},"STRBP is involved in alternative splicing of genes associated with epithelial–mesenchymal transition, including isoform switching of CLSTN1 that induces EMT-like morphology.","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},331933,1790153076,{"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":39,"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":36,"preview_page_count":4},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","RESEARCH ARTICLE  \nSatellite double-stranded RNA induces mesenchymal transition in pancreatic cancer by regulating alternative splicing  \nReceived for publication, March 24, 2023, and in revised form, December 26, 2023 Published, Papers in Press, February 10, 2024, [https://doi.org/10.1016/j.jbc.2024.105742](https://doi.org/10.1016/j.jbc.2024.105742)  \nTakuma Iwata, Takahiro Kishikawa*, Takahiro Seimiya, Genso Notoya, Tatsunori Suzuki, Chikako Shibata,  \nYu Miyakawa, Nariaki Odawara, Kazuyoshi Funato, Eri Tanaka, Mari Yamagami, Kazuma Sekiba, Motoyuki Otsuka, Kazuhiko Koike, and Mitsuhiro Fujishiro  \nFrom the Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Reviewed by members of the JBC Editorial Board. Edited by Ronald Wek  \nHuman satellite II (HSATII), composed of tandem repeats in pericentromeric regions, is aberrantly transcribed in epithelial cancers, particularly pancreatic cancer. Dysregulation of repetitive elements in cancer tissues can facilitate incidental dsRNA formation; however, it remains controversial whether dsRNAs play tumor-promoting or tumor-suppressing roles during cancer progression. Therefore, we focused on the double-stranded formation of HSATII RNA and explored its molecular function. The overexpression of double-stranded HSATII (dsHSATII) RNA promoted mesenchymal-like morphological changes and enhanced the invasiveness of pancreatic cancer cells. We identified an RNA-binding protein, spermatid perinuclear RNA-binding protein (STRBP), which preferentially binds to dsHSATII RNA rather than singlestranded HSATII RNA. The mesenchymal transition of dsHSATII-expressing cells was rescued by STRBP overexpression. Mechanistically, STRBP is involved in the alternative splicing of genes associated with epithelial–mesenchymal transition (EMT). We also confirmed that isoform switching of CLSTN1, driven by dsHSATII overexpression or STRBP depletion, induced EMT-like morphological changes. These findings reveal a novel tumor-promoting function of dsHSATII RNA, inducing EMT-like changes and cell invasiveness, thus enhancing our understanding of the biological significance of aberrant expression of satellite arrays in malignant tumors.  \nRepetitive elements comprise more than half of the human genome and are classified into two types based on their repeating structure: interspersed repetitive DNAs and tandem repeats. While the interspersed repeats are primarily composed of retrotransposons and dispersed throughout the genome, satellite repeats are preferentially located in centromeric and subtelomeric heterochromatin and clustered in long megabase-size arrays (1). Recently, improvements in computational approaches with high-throughput ultralong sequencing by the telomere-to-telomere (T2T) consortium have generated a complete human reference genome map and  \n* For correspondence: Takahiro Kishikawa, [tkishikawa-tky@g.ecc.u-tokyo.ac](tkishikawa-tky@g.ecc.u-tokyo.ac). jp.  \na precise transcriptional and epigenetic landscape of centromeric and pericentromeric regions (2–4). The transcription of pericentromeric satellite arrays is epigenetically silenced under physiological conditions because of the recruitment of chromatin modifiers to maintain heterochromatic status; however, the dysregulation of such satellite array expression has been reported in several malignant diseases (1). Human satellite II (HSATII), a dominant human satellite family located in pericentromeric regions, is highly expressed in pancreatic cancer, but not in normal tissues (5). High HSATII RNA levels were detected in the sera of patients with pancreatic cancer compared to those without cancer (6, 7). HSATII expression is also correlated with poor survival rates in ovarian and colorectal cancers (8, 9). Although HSATII RNAs may not be translated into protein, their oncogenic roles, such as inducing cell division deficiency and chromosomal instability (10), maintaining tumor-assisting immune microenvironment ","cbCaif7YRJpgH2T9","https://ap.wps.com/l/cbCaif7YRJpgH2T9","pdf",5035381,16,"English","# Introduction\n# Results\n# Mechanistic findings\n# Discussion\n# Conclusion","[{\"question\":\"What role does dsHSATII play in pancreatic cancer cells?\",\"answer\":\"dsHSATII overexpression promotes mesenchymal-like morphological changes and enhances the invasiveness of pancreatic cancer cells.\"},{\"question\":\"Which protein binds dsHSATII and what is its functional effect?\",\"answer\":\"STRBP preferentially binds dsHSATII RNA, and STRBP overexpression rescues the mesenchymal transition in dsHSATII-expressing cells.\"},{\"question\":\"How does STRBP mechanistically influence EMT-related changes?\",\"answer\":\"STRBP is involved in alternative splicing of genes associated with epithelial–mesenchymal transition, including isoform switching of CLSTN1 that induces EMT-like morphology.\"}]","Satellite double-stranded RNA induces mesenchymal transition in pancreatic cancer by regulating alternative splicing | PDF",1789995820]