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Despite effective vaccines, no targeted anti-viral therapies exist for HPV or HPV-associated cancers. The study shows LASP1 is upregulated in HPV-positive cervical cancer, correlates with poorer overall survival, and supports oncogenic phenotype growth. HPV E7 represses miR-203 post-transcriptionally, enabling LASP1 expression and tumorigenicity in vivo.",{"@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/e7-mediated-repression-of-mir-203-promotes-lasp1-dependent-proliferation-in-hpv-positive-cervical-cancer/332205/",{"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/e7-mediated-repression-of-mir-203-promotes-lasp1-dependent-proliferation-in-hpv-positive-cervical-cancer/332205.png","ImageObject",300,407,{"name":92,"@type":93},"Maeve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","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 HPV E7 play in regulating LASP1?","Question",{"text":112,"@type":113},"HPV E7 represses miR-203 at the post-transcriptional level. This relief of miR-203 enables higher LASP1 mRNA levels and supports oncogenic behavior.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is LASP1 linked to patient outcomes in HPV-positive cervical cancer?",{"text":117,"@type":113},"LASP1 expression is upregulated in HPV-positive cervical cancer and significantly correlates with poorer overall survival.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is the LASP1 SH3 domain important in HPV-positive cells?",{"text":121,"@type":113},"The study demonstrates that the LASP1 SH3 domain is essential for LASP1-mediated oncogenicity in HPV-positive cervical cancer cells.","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},332205,1790122440,{"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":145,"preview_page_count":4},5909877438554,"https://ap-avatar.wpscdn.com/avatar/5600025385ad2bf12a7?_k=1778553567797529272","[www.nature.com/onc](www.nature.com/onc Oncogene)[ Oncogene](www.nature.com/onc Oncogene)  \nARTICLE OPEN   \nE7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer  \nMolly R. Patterson 1,2,8, Aniek S. Meijers 1,2, Emma L. Ryder 1,2, Louisa M. Wootton3, James A. Scarth 1,2,9, Debra Evans4, Amy L. Turner 1,2, Christopher W. Wasson5, Janne E. Darell1,2, Daisy A. Theobald 1,2, Joseph A. Cogan1,2, Claire D. James6, Miao Wang 1,2,  \nJohn E. Ladbury 1,2, Iain M. Morgan6,7, Adel Samson4, Ethan L. Morgan 1,2,3 ✉ and Andrew Macdonald 1,2 ✉  \n© The Author(s) 2024  \n\n|  | Human papillomaviruses (HPV) are a major cause of malignancy, contributing to ~5% of all human cancers worldwide, including most cervical cancer cases and a growing number of anogenital and oral cancers. The major HPV viral oncogenes, E6 and E7, manipulate many host cellular pathways that promote cell proliferation and survival, predisposing infected cells to malignant transformation. Despite the availability of highly effective vaccines, there are still no specific anti-viral therapies targeting HPV or treatments for HPV-associated cancers. As such, a better understanding of viral-host interactions may allow the identification of novel therapeutic targets. Here, we demonstrate that the actin-binding protein LASP1 is upregulated in cervical cancer and significantly correlates with a poorer overall survival. In HPV positive cervical cancer, LASP1 depletion significantly inhibited the oncogenic phenotype in vitro, whilst having minimal effects in HPV negative cervical cancer cells. Furthermore, we demonstrate that the LASP1 SH3 domain is essential for LASP1-mediated oncogenicity in these cells. Mechanistically, we show that HPV E7 regulates LASP1 at the post-transcriptional level by repressing the expression of miR-203, which negatively regulates LASP1 mRNA levels by binding to its 3’UTR. Finally, we demonstrate that LASP1 expression is required for the growth of HPV positive cervical cancer cells in an in vivo tumourigenicity model. Together, these data demonstrate that HPV induces LASP1 expression to promote |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| proliferation and survival in cervical cancer, thus identifying a potential therapeutic target in these cancers. |  |  |\n|  | Oncogene (2024) 43:2184–2198; [https://doi.org/10.1038/s41388-024-03067-4](https://doi.org/10.1038/s41388-024-03067-4) |  |\n|  |  |  |\n\nINTRODUCTION  \nHigh-risk human papillomavirus (HR-HPV) infection is the underlying cause of almost all cervical cancers and several other anogenital and oropharyngeal cancers [1] . These cancers are predominantly caused by HPV16 and HPV18, with 13 other HRHPV types associated with cancer development [2] . The drivers of HPV-induced proliferation are the viral oncogenes E5, E6 and E7 [3] . During productive infection, HPV E5 induces pro-proliferative EGFR signalling, promotes immune evasion, and functions as a viral-encoded ion channel [4–7] . However, HPV E6 and E7 are the primary oncogenes of viral transformation [3] . The most well characterised function of these oncogenes is the inactivation of the p53 and pRb tumour suppressors, respectively [8–11]; however, recent studies demonstrate that E6 and E7 modulate a plethora of host signalling pathways that have critical functions in cellular transformation [12–19] .  \nLIM and SH3 protein 1 (LASP1) was first identified in metastatic lymph nodes in breast cancer patients [20] . The LASP1 gene is located on chromosome 17q12 in humans and encodes a protein containing an N-terminal LIM domain followed by two actin-  \nbinding sites and a C-terminal SRC homology SH3 domain [21] . This protein architecture allows LASP1 to engage in multiple protein–protein interactions, which may promote cell transformation. For example, the interaction of LASP1 with S100A11 promotes TGFβ-mediated ","cbCaipUG50PbdkWt","https://ap.wps.com/l/cbCaipUG50PbdkWt","pdf",5465331,15,"English","# Introduction\n## Viral oncogenes and host transformation pathways\n## LASP1 biology and links to cancer\n## Study objective and experimental direction\n# Results\n## LASP1 upregulation and survival correlation\n## Functional effects of LASP1 depletion\n## Requirement of LASP1 SH3 domain\n## Mechanism: E7 represses miR-203\n## LASP1 requirement for in vivo growth","[{\"question\":\"What role does HPV E7 play in regulating LASP1?\",\"answer\":\"HPV E7 represses miR-203 at the post-transcriptional level. This relief of miR-203 enables higher LASP1 mRNA levels and supports oncogenic behavior.\"},{\"question\":\"How is LASP1 linked to patient outcomes in HPV-positive cervical cancer?\",\"answer\":\"LASP1 expression is upregulated in HPV-positive cervical cancer and significantly correlates with poorer overall survival.\"},{\"question\":\"Why is the LASP1 SH3 domain important in HPV-positive cells?\",\"answer\":\"The study demonstrates that the LASP1 SH3 domain is essential for LASP1-mediated oncogenicity in HPV-positive cervical cancer cells.\"}]","E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer | PDF",1789997301,38]