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This study clarifies how PRMT5 regulates angiogenesis to enhance lung cancer cell metastasis and defines the associated molecular mechanisms. PRMT5 is overexpressed and hypoxia-induced in lung cancer cells and tissues. Inhibition or silencing PRMT5 disrupts VEGFR/Akt/eNOS phosphorylation, NOS activity, and NO production, reduces HIF-1α expression and stability, and down-regulates VEGF/VEGFR signaling. Findings link PRMT5 with angiogenesis and EMT and support PRMT5 targeting as a therapeutic strategy for lung cancer with abnormal angiogenesis.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/prmt5-facilitates-angiogenesis-and-emt-via-hif-1vegfrakt-signaling-axis-in-lung-cancer/382631/",{"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/prmt5-facilitates-angiogenesis-and-emt-via-hif-1vegfrakt-signaling-axis-in-lung-cancer/382631.png","ImageObject",300,407,{"name":92,"@type":93},"Alex Sinclair","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What triggers PRMT5 expression in lung cancer cells and tissues?","Question",{"text":112,"@type":113},"PRMT5 expression is triggered by hypoxia, and it is overexpressed in lung cancer cells and tissues.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does PRMT5 inhibition affect angiogenic signaling?",{"text":117,"@type":113},"Inhibiting or silencing PRMT5 disrupts phosphorylation of the VEGFR/Akt/eNOS angiogenic signaling pathway, reduces NOS activity, and decreases NO production.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the proposed relationship between PRMT5, HIF-1α, and EMT in lung cancer?",{"text":121,"@type":113},"PRMT5 activity reduces HIF-1α expression and stability, leading to down-regulation of VEGF/VEGFR signaling, and PRMT5 promotes epithelial-mesenchymal transition (EMT) through the HIF-1α/VEGFR/Akt/eNOS signaling axis.","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},382631,1790326078,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"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},1099523882182,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","[www.aging-us.com](www.aging-us.com) AGING 2023, Vol. 15, No. 13  \nResearch Paper  \nPRMT5 facilitates angiogenesis and EMT via HIF-1α/VEGFR/Akt signaling axis in lung cancer  \nYonghua Zheng1,*, Huaxia Ji1,*, Wulin Yi1,*, Zhanjun Chen1, Xiaobiao Hu1, Jie Zhou2, Yang Wang3, Xiao Zheng1  \n1 Department of Pulmonary Medicine, Shanghai Jinshan Tinglin Hospital, Shanghai, P. R. China 2 Dapartment of Pulmonary and Critical Care Medicine, Minhang Hospital, Fudan University, P. R. China 3 Department of Emergency, The 8th People's Hospital of Shanghai, Shanghai, P. R. China  \n*Equal contribution  \nCorrespondence to: Yang Wang, Xiao Zheng; [email:](email: WYHGL@126.com)[ ](email: WYHGL@126.com)[WYHGL@126.com](email: WYHGL@126.com), [https://orcid.org/0009-0000-7831-5297](https://orcid.org/0009-0000-7831-5297); [189187200111@189.cn](189187200111@189.cn), [https://orcid.org/0009-0002-8125-4274](https://orcid.org/0009-0002-8125-4274)  \nKeywords: PRMT5, HIF-1α, EMT, angiogenesis, lung cancer  \nReceived: March 21, 2023 Accepted: May 24, 2023 Published: July 3, 2023  \nCopyright: © 2023 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nABSTRACT  \nAbnormal angiogenesis is a critical factor in tumor growth and metastasis, and protein arginine methyltransferase 5 (PRMT5), a prominent type II enzyme, is implicated in various human cancers. However, the precise role of PRMT5 in regulating angiogenesis to promote lung cancer cell metastasis and the underlying molecular mechanisms are not fully understood. Here, we show that PRMT5 is overexpressed in lung cancer cells and tissues, and its expression is triggered by hypoxia. Moreover, inhibiting or silencing PRMT5 disrupts the phosphorylation of the VEGFR/Akt/eNOS angiogenic signaling pathway, NOS activity, and NO production. Additionally, inhibiting PRMT5 activity reduces HIF-1α expression and stability, resulting in the down-regulation of the VEGF/VEGFR signaling pathway. Our findings indicate that PRMT5 promotes lung cancer epithelial-mesenchymal transition (EMT), which might be possibly through controlling the HIF-1α/VEGFR/Akt/eNOS signaling axis. Our study provides compelling evidence of the close association between PRMT5 and angiogenesis/EMT and highlights the potential of targeting PRMT5 activity as a promising therapeutic approach for treating lung cancer with abnormal angiogenesis.  \nINTRODUCTION  \nLung cancer is a prevalent and dangerous cancer that starts in the lungs and is one of the leading causes of cancer-related deaths worldwide, accounting for nearly one in five deaths caused by this cancer. Lung cancer can be divided into two main types: small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) [1–3] . NSCLC, which includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, is the more common type of lung cancer, accounting for about 80-85% of all cases [4]. SCLC accounts for the remaining 15-20% of cases. Therefore, it is crucial to investigate the molecular mechanisms underlying lung cancer development to uncover potential therapeutic targets and improve lung cancer treatment in its early stages.  \nAngiogenesis is the process of forming new blood vessels from existing vessels. In normal physiology, angiogenesis is a natural and regulated process during growth, wound healing, and embryonic development [5, 6] . However, in human cancers, angiogenesis is often abnormal and uncontrolled. Cancer cells require a blood supply to grow and spread, and they stimulate the growth of new blood vessels to meet their metabolic needs [7] . This uncontrolled angiogenesis creates a network of blood vessels that nourish the cancer cells and supply oxygen and nutrients, enabling them to grow and spread to other parts of the human body. A growing body of evidence sug","cbCaihIJcjzkBOT4","https://ap.wps.com/l/cbCaihIJcjzkBOT4","pdf",1754472,16,"English","# Abstract\n# Introduction\n# Results\n## PRMT5 is highly expressed in human lung cancer","[{\"question\":\"What triggers PRMT5 expression in lung cancer cells and tissues?\",\"answer\":\"PRMT5 expression is triggered by hypoxia, and it is overexpressed in lung cancer cells and tissues.\"},{\"question\":\"How does PRMT5 inhibition affect angiogenic signaling?\",\"answer\":\"Inhibiting or silencing PRMT5 disrupts phosphorylation of the VEGFR/Akt/eNOS angiogenic signaling pathway, reduces NOS activity, and decreases NO production.\"},{\"question\":\"What is the proposed relationship between PRMT5, HIF-1α, and EMT in lung cancer?\",\"answer\":\"PRMT5 activity reduces HIF-1α expression and stability, leading to down-regulation of VEGF/VEGFR signaling, and PRMT5 promotes epithelial-mesenchymal transition (EMT) through the HIF-1α/VEGFR/Akt/eNOS signaling axis.\"}]","PRMT5 facilitates angiogenesis and EMT via HIF-1α/VEGFR/Akt signaling axis in lung cancer | PDF",1790251431]