{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:02:03Z","timestamp":1788804123821,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,6]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Cancer cachexia (CCx) is a complex and multi\u2010organ wasting syndrome characterized by substantial weight loss and poor prognosis. An improved understanding of the mechanisms involved in the onset and progression of cancer cachexia is essential. How microRNAs contribute to the clinical manifestation and progression of CCx remains elusive. The aim of this study was to identify specific miRNAs related to organ\u2010specific CCx and explore their functional role in humans.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n miRNA patterns in serum and in cachexia target organs (liver, muscle and adipose tissue) from weight stable (\n N<\/jats:italic>\n \u00a0\u2264\u00a012) and cachectic patients (\n N<\/jats:italic>\n \u00a0\u2264\u00a023) with gastrointestinal cancer were analysed. As a first step, a miRNA array (158 miRNAs) was performed in pooled serum samples. Identified miRNAs were validated in serum and corresponding tissue samples. Using\n in silico<\/jats:italic>\n prediction, related genes were identified and evaluated. The findings were confirmed\n in vitro<\/jats:italic>\n by siRNA knock\u2010down experiments in human visceral preadipocytes and C2C12 myoblast cells and consecutive gene expression analyses.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Validating the results of the array, a 2\u2010fold down\u2010regulation of miR\u2010122\u20105p (\n P<\/jats:italic>\n \u00a0=\u00a00.0396) and a 4.5\u2010fold down\u2010regulation of miR\u2010194\u20105p (\n P<\/jats:italic>\n \u00a0<\u00a00.0001) in serum of CCx patients in comparison with healthy controls were detected. Only miR\u2010122\u20105p correlated with weight loss and CCx status (\n P<\/jats:italic>\n \u00a0=\u00a00.0367). Analysing corresponding tissues six muscle and eight visceral adipose tissue (VAT) cachexia\u2010associated miRNAs were identified. miR\u201027b\u20103p, miR\u2010375 and miR\u2010424\u20105p were the most consistently affected miRNAs in tissues of CCx patients correlating negatively with the severity of body weight loss (\n P<\/jats:italic>\n \u00a0=\u00a00.0386,\n P<\/jats:italic>\n \u00a0=\u00a00.0112 and\n P<\/jats:italic>\n \u00a0=\u00a00.0075, respectively). We identified numerous putative target genes of the miRNAs in association with muscle atrophy and lipolysis pathways. Knock\u2010down experiments in C2C12 myoblast cells revealed an association of miR\u201027b\u20103p and the\n in silico<\/jats:italic>\n predicted atrophy\u2010related target genes\n IL\u201015<\/jats:italic>\n and\n TRIM63<\/jats:italic>\n . Both were up\u2010regulated in miR\u201027b\u20103p knock\u2010down cells (\n P<\/jats:italic>\n \u00a0<\u00a00.05). Concordantly, in muscle tissue of CCx individuals, significant higher expression levels of\n IL\u201015<\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0=\u00a00.0237) and\n TRIM63<\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0=\u00a00.0442) were detected. miR\u2010424\u20105p was identified to regulate the expression of lipase genes. Knock\u2010down experiments in human visceral preadipocytes revealed an inverse association of miR\u2010424\u20105p with its predicted target genes\n LIPE, PNPLA2, MGLL<\/jats:italic>\n and\n LPL<\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0<\u00a00.01).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The identified miRNAs, in particular miR\u2010122\u20105p, miR\u201027b\u20103p, miR\u2010375 and miR\u2010424\u20105p, represent features of human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the regulation of catabolic signals. Further studies are needed to explore the potential of the identified miRNAs as a screening tool for early detection of cancer cachexia.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13224","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T04:09:30Z","timestamp":1680754170000},"page":"1381-1394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Specific miRNAs are associated with human cancer cachexia in an organ\u2010specific manner"],"prefix":"10.1002","volume":"14","author":[{"given":"Tanja","family":"Krauss","sequence":"first","affiliation":[{"name":"Else Kr\u00f6ner\u2010Fresenius Center for Nutritional Medicine, School of Life Sciences Technical University of Munich Freising\u2010Weihenstephan Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Heisz","sequence":"additional","affiliation":[{"name":"Else Kr\u00f6ner\u2010Fresenius Center for Nutritional Medicine, School of Life Sciences Technical University of Munich Freising\u2010Weihenstephan Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Honecker","sequence":"additional","affiliation":[{"name":"Else Kr\u00f6ner\u2010Fresenius Center for Nutritional Medicine, School of Life Sciences Technical University of Munich Freising\u2010Weihenstephan Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Prokopchuk","sequence":"additional","affiliation":[{"name":"Department of Surgery, Klinikum rechts der Isar University Hospital of the Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Martignoni","sequence":"additional","affiliation":[{"name":"Department of Surgery, Klinikum rechts der Isar University Hospital of the Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus\u2010Peter","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Klinikum rechts der Isar University Hospital of the Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Claussnitzer","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard Cambridge Massachusetts USA"},{"name":"Harvard Medical School Harvard University Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hauner","sequence":"additional","affiliation":[{"name":"School of Medicine, Institute of Nutritional Medicine Technical University of Munich Munich Germany"},{"name":"ZIEL Institute for Food and Health Technical University of Munich Freising\u2010Weihenstephan Germany"},{"name":"Else Kr\u00f6ner\u2010Fresenius Center for Nutritional Medicine, School of 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