[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-349407-105":59,"doc-detail-349407-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","rapid-evolution-of-lncrnas-introduces-novel-regulatory-inputs-into-ancestral-cancer-pathways","Rapid evolution of lncRNAs introduces novel regulatory inputs into ancestral cancer pathways","","Human long noncoding RNAs (lncRNAs) are often lineage specific and increasingly linked to cancer, but how their oncogenic relevance evolved remains unclear. The study tests whether new cancer-associated lncRNAs arise through adaptive refinement or through neutral by-products of transcriptomic complexity under weak selection. Newly evolved primate lncRNAs emerge via increased transcription, then expand and incorporate genomic fragments, integrating into conserved cancer pathways such as the AMPK/ferroptosis network. Validation uses MIR497HG and supports constructive neutral evolution.",{"@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/rapid-evolution-of-lncrnas-introduces-novel-regulatory-inputs-into-ancestral-cancer-pathways/349407/",{"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/rapid-evolution-of-lncrnas-introduces-novel-regulatory-inputs-into-ancestral-cancer-pathways/349407.png","ImageObject",300,407,{"name":92,"@type":93},"Ben ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-22",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 major question does the study address about lncRNAs and cancer?","Question",{"text":112,"@type":113},"It examines how the evolutionary origins of lncRNAs’ oncogenic relevance arise, specifically whether novel roles come from adaptive processes or from neutral by-products under weak selection.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do the authors propose newly evolved cancer-associated lncRNAs arise?",{"text":117,"@type":113},"They arise through a stepwise process initiated by increased transcriptional activity, followed by sequence expansion once expression exceeds a threshold.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence supports the proposed model, and which pathway is highlighted?",{"text":121,"@type":113},"The model is validated using MIR497HG, which expanded and integrated into the ancient AMPK/ferroptosis network in humans, affecting oncogenesis.","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},349407,1790293735,{"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},2336478951081,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","EVOLUTIONARY BIOLOGY  \nRapid evolution of lncRNAs introduces novel regulatory inputs into ancestral cancer pathways  \nLi Sun1,2†, Chuan Dong3†, Dandan Hong1,2, Meng-Ze Du4, Shengqian Xia5, Hao Fan6, Michael Lynch7, Yongmei Li1,2*, Wen Wei7*  \nA substantial fraction of human long noncoding RNAs (lncRNAs) are lineage specific and increasingly implicated in cancer, yet the evolutionary origins of their oncogenic relevance remain unclear. It is unknown whether such roles arise through adaptive refinement or as incidental by-products of transcriptomic complexity under weak selection. Here, we show that newly evolved cancer-associated lncRNAs, predominantly of primate origin, arise through a stepwise process initiated by increased transcriptional activity. Once expression surpasses a threshold, these lncRNAs undergo sequence expansion, with 73.3% incorporating external or local genomic fragments, facilitating integration into deeply conserved cancer-related pathways. We validate this model through MIR497HG, which originated near amicroRNA in the human-macaque ancestor, and subsequently expanded and integrated into the ancient AMPK (adenosine monophosphate–activated protein kinase)/ferroptosis network in humans, influencing oncogenesis. Collectively, our findings support a model in which weak selection permits neutral transcriptional innovations to persist and gradually infiltrate ancient regulatory architectures, consistent with constructive neutral evolution.  \ncopyright © 2026 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S.  \nGovernment Works. distributed under a creative commons Attribution noncommercial license 4.0 (cc BY-nc) .  \nINTRODUCTION  \nLong noncoding RNAs (lncRNAs) have emerged as notable modulators ofoncogenic and tumor-suppressive pathways (1–3), influencing diverse cellular functions such as proliferation, metastasis, and immune evasion. Although many of these roles co-opt regulatory mechanisms with deep evolutionary origins traceable to early metazoans (4), the lncRNAs implicated in modulating cancer susceptibility often appear to be of more recent evolutionary derivation—frequently restricted to mammals (5) . This phylogenetic restriction of recently evolved lncRNA regulators may underlie, at least in part, the elevated frequency and unique spectrum of cancers observed in humans and, to a lesser extent, in other primates. Such lineage-specific regulatory innovations likely interact with conserved cellular processes in ways that introduce novel susceptibilities to dysregulation.  \nFor instance, the human-specific lncRNA LINC00662 (5) modulates several ancient pathways in various cancers, such as the Wnt/β-catenin signaling pathway in hepatocellular carcinoma (6), the Hippo-YAP1 pathway in gastric cancer (7), and the MAPK/p38 pathway in ovarian cancer (8) . The three pathways originated before the divergence of metazoans [~758 million years ago (Ma)], holozoans (~894 Ma), and opisthokonts (~ 1275 Ma) (9, 10). Another example is the lncRNA H19, which emerged before the divergence of primates and mice, around 90 Ma (5). H19 participates in the ancient eukaryotic PI3K-Akt-mTOR pathway [originating around 1530 Ma (9, 10)] by promoting the phosphorylation of PI3K and AKT, ultimately inhibiting apoptosis and autophagy (11, 12).  \n1department of Gynaecology and Obstetrics, the Second hospital of tianjin Medical University, tianjin 300211, china. 2department of Pathogen Biology, School of Basic Medical Science, tianjin Medical University, tianjin 300070, china. 3School of Forestry and Biotechnology, Zhejiang A&F University, hangzhou 311300, china. 4School of healthcare technology, chengdu neusoft University, chengdu 611844, china. 5department of ecology and evolution, the University of chicago, chicago, il 60637, USA. 6department of Medicine, the University of chicago, chicago, il 60637, USA. 7Biodesign center for Mechanisms of evolution, Ar","cbCaivYmXpnO2V0l","https://ap.wps.com/l/cbCaivYmXpnO2V0l","pdf",4341082,17,"English","# Introduction\n## Lineage-specific lncRNA roles in oncogenesis\n## Deep evolutionary origins of cancer-related pathways\n## Examples: LINC00662 and H19\n## Primate noncoding DNA as raw material for new lncRNAs\n## Relaxed selection and TE-driven innovation in lncRNAs","[{\"question\":\"What major question does the study address about lncRNAs and cancer?\",\"answer\":\"It examines how the evolutionary origins of lncRNAs’ oncogenic relevance arise, specifically whether novel roles come from adaptive processes or from neutral by-products under weak selection.\"},{\"question\":\"How do the authors propose newly evolved cancer-associated lncRNAs arise?\",\"answer\":\"They arise through a stepwise process initiated by increased transcriptional activity, followed by sequence expansion once expression exceeds a threshold.\"},{\"question\":\"What evidence supports the proposed model, and which pathway is highlighted?\",\"answer\":\"The model is validated using MIR497HG, which expanded and integrated into the ancient AMPK/ferroptosis network in humans, affecting oncogenesis.\"}]","Rapid evolution of lncRNAs introduces novel regulatory inputs into ancestral cancer pathways | PDF",1790083171,43]