[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-detail-332057-en":59,"doc-seo-332057-105":80},{"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":5,"data":60},{"doc_id":61,"user_id":62,"nickname":63,"user_avatar":64,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":66,"doc_content":67,"file_id":68,"file_url":69,"file_type":70,"file_size":71,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":72,"language_code":73,"site_id":74,"html_lang":73,"table_of_contents":75,"faqs":76,"seo_title":77,"seo_description":66,"update_tm":78,"read_time":79,"preview_page_count":4},332057,4810365810221,"Aurora","https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","RRP8, associated with immune infiltration, is a prospective therapeutic target in hepatocellular carcinoma","Ribosomal RNA Processing 8 (RRP8) is a nucleolar Rossman fold-like methyltransferase with increased expression in many malignant tumors, yet its role in hepatocellular carcinoma (HCC) remains unclear. This study evaluates how RRP8 relates to prognosis and immune infiltration, and investigates its pathological function and mechanism in HCC. Multi-database analyses, enrichment, ssGSEA, Cox regression, and a survival nomogram are integrated with doxycycline-inducible shRNA knockdown and CRISPR-Cas9 knockout for functional validation.","Journal of Cancer Research and Clinical Oncology (2024) 150:245  \n[https://doi.org/10.1007/s00432-024-05756-9](https://doi.org/10.1007/s00432-024-05756-9)  \nRRP8, associated with immune infiltration, is a prospective therapeutic target in hepatocellular carcinoma  \nKai You1,2,3 · Xingxing Du1,2,3 · Yunzheng Zhao2 · Fukai Wen2 · Zhaoyang Lu2 · Huitao Fan1,2,3  \nReceived: 17 February 2024 / Accepted: 22 April 2024 / Published online: 9 May 2024 © The Author(s) 2024  \nAbstract  \nBackground Ribosomal RNA Processing 8 (RRP8) is a nucleolar Rossman fold-like methyltransferase that exhibits increased expression in many malignant tumours. However, the role of RRP8 in hepatocellular carcinoma (HCC) is still uncertain. We explored the relationships between RRP8 and prognosis and immune infiltration, as well as the putative pathological function and mechanism of RRP8 in HCC.  \nMethods Analysis of RRP8 expression across cancers was performed by using multiple databases. Associations between RRP8 expression and clinicopathological factors were further examined. Gene enrichment analysis was used to identify various putative biological activities and regulatory networks of RRP8 in HCC. The relationship between RRP8 expression and immune infiltration was confirmed by single-sample gene set enrichment analysis (ssGSEA) . Univariate and multivariate Cox regression analyses were conducted to assess the impact of clinical variables on patient outcomes. Furthermore, a nomogram was constructed to estimate survival probability based on multivariate Cox regression analysis. Functional validation of RRP8 in HCC was performed with two different systems: doxycycline-inducible shRNA knockdown and CRISPR-Cas9 knockout. Results RRP8 was markedly overexpressed in HCC clinical specimens compared to adjacent normal tissues. Further analysis demonstrated that RRP8 was directly connected to multiple clinical characteristics and strongly associated with various immune markers in HCC. Moreover, elevated RRP8 expression indicated an unfavourable prognosis. Our functional studies revealed that both knockdown and knockout of RRP8 dramatically attenuated liver cancer cells to proliferate and migrate. Knockout of RRP8 decreased the phosphorylation of MEK1/2 and β-catenin-(Y654) signalling pathway components; downregulated downstream signalling effectors, including Cyclin D1 and N-cadherin; and upregulated E-cadherin.  \nConclusions RRP8 is strongly implicated in immune infiltration and could be a potential therapeutic target in HCC.  \nKeywords RRP8 · Targeted therapy · Prognosis · Immune infiltration · Hepatocellular carcinoma  \n* Huitao Fan [huitaofan@hrbmu.edu.cn](huitaofan@hrbmu.edu.cn)  \n1 NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China  \n2 Key Laboratory of Hepatosplenic Surgery of Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China  \n3 Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China  \nIntroduction  \nGlobally, 841,000 new cases of HCC are diagnosed each year, and 782,000 deaths are caused by the disease (Villanueva and Longo 2019) . HCC development is influenced by a number of important factors, including hepatitis B infection, hepatitis C infection and exposure to aflatoxintainted foods (Howell et al. 2021). HCC is typically treated with surgery; however, the propensity for recurrence and metastasis makes it very challenging to successfully treat (Johnson et al. 2022) . Hence, novel and useful biomarkers or targeted therapies are urgently needed to diagnose HCC early and treat it effectively (Bruix et al. 2016 ; Frau et al. 2010 ; Gu et al. 2023) .  \nThe RRP8 protein is located mainly in the nucleus and harbours highly conserved methyltransferase-specific  \nmotifs (Bousquet-Antonelli et al. 2000) . It forms an energy-de","cbCaii8s1Z3y5R3F","https://ap.wps.com/l/cbCaii8s1Z3y5R3F","pdf",5676930,"English","en",105,"# Abstract\n# Introduction\n## Background of HCC and rationale\n## RRP8 biology and knowledge gap\n# Materials and methods\n## TCGA data analysis\n## Patients and clinical specimens","[{\"question\":\"What is the main biological focus of this study?\",\"answer\":\"The study focuses on RRP8 and how it is linked to immune infiltration and clinical outcomes in hepatocellular carcinoma.\"},{\"question\":\"How do the methods assess prognosis and immune infiltration?\",\"answer\":\"They analyze RRP8 expression across cancers, relate it to clinicopathological factors, use enrichment analysis and ssGSEA to connect expression with immune markers, and apply Cox regression with a nomogram for survival estimation.\"},{\"question\":\"What functional effects does RRP8 manipulation have in HCC models?\",\"answer\":\"Doxycycline-inducible shRNA knockdown and CRISPR-Cas9 knockout markedly reduce liver cancer cell proliferation and migration, and alter MEK1/2 and β-catenin-(Y654) signaling pathway components.\"}]","RRP8, associated with immune infiltration, is a prospective therapeutic target in hepatocellular carcinoma | PDF",1789996514,48,{"code":4,"msg":81,"data":82},"ok",{"site_id":74,"language":73,"slug":83,"title":65,"keywords":84,"description":66,"schema_data":85,"social_meta":139,"head_meta":141,"extra_data":143,"updated_unix":144},"rrp8-associated-with-immune-infiltration-is-a-prospective-therapeutic-target-in-hepatocellular-carcinoma","",{"@graph":86,"@context":138},[87,101,121],{"@type":88,"itemListElement":89},"BreadcrumbList",[90,94,96,99],{"item":91,"name":92,"@type":93,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":95,"name":9,"@type":93,"position":14},"https://docshare.wps.com/document/",{"item":97,"name":40,"@type":93,"position":98},"https://docshare.wps.com/document/research-report/",3,{"item":100,"name":65,"@type":93,"position":19},"https://docshare.wps.com/document/rrp8-associated-with-immune-infiltration-is-a-prospective-therapeutic-target-in-hepatocellular-carcinoma/332057/",{"url":100,"name":65,"@type":102,"image":103,"author":108,"headline":65,"publisher":110,"fileFormat":113,"inLanguage":73,"description":66,"dateModified":114,"datePublished":115,"encodingFormat":113,"isAccessibleForFree":116,"interactionStatistic":117},"DigitalDocument",{"url":104,"@type":105,"width":106,"height":107},"https://docshare.wps.com/thumbnails/rrp8-associated-with-immune-infiltration-is-a-prospective-therapeutic-target-in-hepatocellular-carcinoma/332057.png","ImageObject",300,407,{"name":63,"@type":109},"Person",{"url":91,"name":111,"@type":112},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":118,"interactionType":119,"userInteractionCount":52},"InteractionCounter",{"@type":120},"ViewAction",{"@type":122,"mainEntity":123},"FAQPage",[124,130,134],{"name":125,"@type":126,"acceptedAnswer":127},"What is the main biological focus of this study?","Question",{"text":128,"@type":129},"The study focuses on RRP8 and how it is linked to immune infiltration and clinical outcomes in hepatocellular carcinoma.","Answer",{"name":131,"@type":126,"acceptedAnswer":132},"How do the methods assess prognosis and immune infiltration?",{"text":133,"@type":129},"They analyze RRP8 expression across cancers, relate it to clinicopathological factors, use enrichment analysis and ssGSEA to connect expression with immune markers, and apply Cox regression with a nomogram for survival estimation.",{"name":135,"@type":126,"acceptedAnswer":136},"What functional effects does RRP8 manipulation have in HCC models?",{"text":137,"@type":129},"Doxycycline-inducible shRNA knockdown and CRISPR-Cas9 knockout markedly reduce liver cancer cell proliferation and migration, and alter MEK1/2 and β-catenin-(Y654) signaling pathway components.","https://schema.org",{"og:url":100,"og:type":140,"og:title":65,"og:site_name":111,"og:description":66},"article",{"robots":142,"canonical":100},"index,follow",{"doc_id":61,"site_id":74},1790176387]