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Total RNA from 360 chronic hepatitis C (CH), 43 HCV-infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues was profiled using microarrays and machine learning.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/analysis-of-carcinogenic-involvement-of-microrna-pattern-in-peripheral-non-cancerous-tissues-and-chronic-viral-liver-injury/332274/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/analysis-of-carcinogenic-involvement-of-microrna-pattern-in-peripheral-non-cancerous-tissues-and-chronic-viral-liver-injury/332274.png","ImageObject",300,407,{"name":42,"@type":43},"Noah","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",5,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What study design and tissue sources were used to analyze miRNA patterns?","Question",{"text":63,"@type":64},"Total RNA was extracted from 360 chronic hepatitis C (CH), 43 HCV-infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues, then miRNA expression patterns were analyzed using microarray and machine learning.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did miRNA expression differ with age between CH and SNT?",{"text":68,"@type":64},"No age-dependent changes were observed in miRNA expression in disease-specific comparisons; however, miRNA expression differed among the 50-, 60-, and 70-year age groups between CH and SNT.",{"name":70,"@type":61,"acceptedAnswer":71},"Which miRNAs were linked to hepatocarcinogenesis beyond liver fibrosis effects?",{"text":72,"@type":64},"Among the 55 miRNAs with significant CH versus SNT differences, 34 also differed significantly even when accounting for the degree of liver fibrosis, and additional miRNAs whose expression did not affect liver fibrosis were also found to be involved in carcinogenesis.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332274,1790537756,{"code":4,"msg":82,"data":83},"success",{"doc_id":79,"user_id":84,"nickname":42,"user_avatar":85,"doc_module":4,"category_id":86,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":87,"file_id":88,"file_url":89,"file_type":90,"file_size":91,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":92,"language":93,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":94,"faqs":95,"seo_title":96,"seo_description":12,"update_tm":97,"read_time":98,"preview_page_count":4},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780",8,"Article  \nAnalysis of Carcinogenic Involvement of MicroRNA Pattern in Peripheral Non-Cancerous Tissues and Chronic Viral  \nLiver Injury  \nTomohiro Umezu 1, Tomoya Mori 2, Hidenori Toyoda 3, Kohsuke Kanekura 1, Akihiro Tamori 4, Takahiro Ochiya 5, Masahiko Kuroda 1, Tatsuya Akutsu 2 and Yoshiki Murakami 1,6, *  \nCitation: Umezu, T.; Mori, T.; Toyoda, H.; Kanekura, K.; Tamori, A.; Ochiya, T.; Kuroda, M.; Akutsu, T.; Murakami, Y. Analysis of Carcinogenic Involvement of MicroRNA Pattern in Peripheral Non-Cancerous Tissues and Chronic Viral Liver Injury. Int. J. Mol. Sci. 2024, 25, 7858. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25147858](doi.org/10.3390/ijms25147858)  \nAcademic Editor: Peter Schemmer  \nReceived: 31 May 2024  \nRevised: 11 July 2024  \nAccepted: 15 July 2024  \nPublished: 18 July 2024  \n1 Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan; [t_umezu@tokyo-med.ac.jp](t_umezu@tokyo-med.ac.jp) (T.U.); [kanekura@tokyo-med.ac.jp](kanekura@tokyo-med.ac.jp) (K.K.); [kuroda@tokyo-med.ac.jp](kuroda@tokyo-med.ac.jp) (M.K.)  \n2 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan; [tmori@kuicr.kyoto-u.ac.jp](tmori@kuicr.kyoto-u.ac.jp) (T.M.); [takutsu@kuicr.kyoto-u.ac.jp](takutsu@kuicr.kyoto-u.ac.jp) (T.A.)  \n3 Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8502, Japan; [hmtoyoda@spice.ocn.ne.jp](hmtoyoda@spice.ocn.ne.jp)  \n4 Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; [tamori-a@omu.ac.jp](tamori-a@omu.ac.jp)  \n5 Institution of Medical Science, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; [tochiya@tokyo-med.ac.jp](tochiya@tokyo-med.ac.jp)  \n6 Department of Dentistry, Asahi University, 3-23 Hashimoto-cho, Gifu 500-8523, Japan  \n* [Correspondence: yoshikim@tokyo-med.ac.jp](Correspondence: yoshikim@tokyo-med.ac.jp); Tel.: +81-3-3351-6141  \nAbstract: Risk factors for hepatocarcinogenesis include chronic inflammation due to viral infection, liver fibrosis, and aging. In this study, we separated carcinogenic and non-carcinogenic cases due to hepatitis C virus (HCV) infection, aiming to comprehensively analyze miRNA expression in liver tissues by age, and identify factors that contribute to carcinogenesis. Total RNA was extracted from 360 chronic hepatitis C (CH), 43 HCV infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues. MicroRNA (miRNA) expression patterns were analyzed using microarray. Using machine learning, we extracted characteristic miRNA expression patterns for each disease and age. There were no age-dependent changes in miRNA expression in the disease-specific comparisons; however, miRNA expression differed among the age groups of 50, 60, and 70 years of age between CH and SNT. The expression of miRNA was different between SNT and HCC only in patients in their 70s. Of the 55 miRNAs with significant differences in expression between CH and SNT, 34 miRNAs showed significant differences in expression even in the degree of liver fibrosis. The observation that miRNAs involved in hepatocarcinogenesis differ at different ages suggests that the mechanisms of carcinogenesis differ by age group as well. We also found that many miRNAs whose expression did not affect liver fibrosis were involved in carcinogenesis. These findings are expected to define biomarkers for detection of HCC at early stage, and develop novel therapeutic targets for HCC.  \nKeywords: miRNA; hepatocellular carcinoma; HCV; surrounding non-tumor tissues; chronic hepatitis  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses","cbCaiiY3VAnLiQwf","https://ap.wps.com/l/cbCaiiY3VAnLiQwf","pdf",2620553,13,"English","# Abstract\n# Introduction","[{\"question\":\"What study design and tissue sources were used to analyze miRNA patterns?\",\"answer\":\"Total RNA was extracted from 360 chronic hepatitis C (CH), 43 HCV-infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues, then miRNA expression patterns were analyzed using microarray and machine learning.\"},{\"question\":\"How did miRNA expression differ with age between CH and SNT?\",\"answer\":\"No age-dependent changes were observed in miRNA expression in disease-specific comparisons; however, miRNA expression differed among the 50-, 60-, and 70-year age groups between CH and SNT.\"},{\"question\":\"Which miRNAs were linked to hepatocarcinogenesis beyond liver fibrosis effects?\",\"answer\":\"Among the 55 miRNAs with significant CH versus SNT differences, 34 also differed significantly even when accounting for the degree of liver fibrosis, and additional miRNAs whose expression did not affect liver fibrosis were also found to be involved in carcinogenesis.\"}]","Analysis of Carcinogenic Involvement of MicroRNA Pattern in Peripheral Non-Cancerous Tissues and Chronic Viral Liver Injury | PDF",1789997618,33,{"code":4,"msg":82,"data":100},[101,105,109,113,117,122,127,130,135,138,142],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":106,"show_sort_weight":107,"slug":108},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":110,"show_sort_weight":111,"slug":112},"Exam",70,"exam",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":114,"show_sort_weight":115,"slug":116},"Comic",60,"comic",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":119,"show_sort_weight":120,"slug":121},6,"Technology",50,"technology",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":125,"slug":126},7,"Healthcare",40,"healthcare",{"id":86,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":128,"slug":129},30,"research-report",{"id":131,"doc_module":4,"doc_module_name":25,"category_name":132,"show_sort_weight":133,"slug":134},9,"Religion & Spirituality",20,"religion-spirituality",{"id":133,"doc_module":4,"doc_module_name":25,"category_name":136,"show_sort_weight":133,"slug":137},"World Cup","world-cup",{"id":139,"doc_module":4,"doc_module_name":25,"category_name":140,"show_sort_weight":139,"slug":141},10,"Lifestyle","lifestyle",{"id":143,"doc_module":4,"doc_module_name":25,"category_name":144,"show_sort_weight":55,"slug":145},19,"General","general"]