FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1564746483> ?p ?o ?g. }

• W1564746483 abstract "Evidence from cachectic cancer patients and animal models of cancer cachexia supports the involvement of Forkhead box O (FoxO) transcription factors in driving cancer-induced skeletal muscle wasting. However, the genome-wide gene networks and associated biological processes regulated by FoxO during cancer cachexia are unknown. We hypothesize that FoxO is a central upstream regulator of diverse gene networks in skeletal muscle during cancer that may act coordinately to promote the wasting phenotype. To inhibit endogenous FoxO DNA-binding, we transduced limb and diaphragm muscles of mice with AAV9 containing the cDNA for a dominant negative (d.n.) FoxO protein (or GFP control). The d.n.FoxO construct consists of only the FoxO3a DNA-binding domain that is highly homologous to that of FoxO1 and FoxO4, and which outcompetes and blocks endogenous FoxO DNA binding. Mice were subsequently inoculated with Colon-26 (C26) cells and muscles harvested 26 days later. Blocking FoxO prevented C26-induced muscle fiber atrophy of both locomotor muscles and the diaphragm and significantly spared force deficits. This sparing of muscle size and function was associated with the differential regulation of 543 transcripts (out of 2,093) which changed in response to C26. Bioinformatics analysis of upregulated gene transcripts that required FoxO revealed enrichment of the proteasome, AP-1 and IL-6 pathways, and included several atrophy-related transcription factors, including Stat3, Fos, and Cebpb. FoxO was also necessary for the cancer-induced downregulation of several gene transcripts that were enriched for extracellular matrix and sarcomere protein-encoding genes. We validated these findings in limb muscles and the diaphragm through qRT-PCR, and further demonstrate that FoxO1 and/or FoxO3a are sufficient to increase Stat3, Fos, Cebpb, and the C/EBPβ target gene, Ubr2. Analysis of the Cebpb proximal promoter revealed two bona fide FoxO binding elements, which we further establish are necessary for Cebpb promoter activation in response to IL-6, a predominant cytokine in the C26 cancer model. These findings provide new evidence that FoxO-dependent transcription is a central node controlling diverse gene networks in skeletal muscle during cancer cachexia, and identifies novel candidate genes and networks for further investigation as causative factors in cancer-induced wasting." @default.
• W1564746483 created "2016-06-24" @default.
• W1564746483 creator A5011130785 @default.
• W1564746483 creator A5040411148 @default.
• W1564746483 creator A5045340664 @default.
• W1564746483 creator A5046131249 @default.
• W1564746483 creator A5060957121 @default.
• W1564746483 creator A5071830667 @default.
• W1564746483 creator A5084077383 @default.
• W1564746483 date "2014-12-01" @default.
• W1564746483 modified "2023-10-18" @default.
• W1564746483 title "Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia" @default.
• W1564746483 cites W1620997626 @default.
• W1564746483 cites W1967293715 @default.
• W1564746483 cites W1968862012 @default.
• W1564746483 cites W1972470375 @default.
• W1564746483 cites W1983660080 @default.
• W1564746483 cites W1985238823 @default.
• W1564746483 cites W1985327273 @default.
• W1564746483 cites W1985534077 @default.
• W1564746483 cites W1989496908 @default.
• W1564746483 cites W1990183651 @default.
• W1564746483 cites W1996634559 @default.
• W1564746483 cites W1997014674 @default.
• W1564746483 cites W1997155298 @default.
• W1564746483 cites W2001061424 @default.
• W1564746483 cites W2003779663 @default.
• W1564746483 cites W2014582629 @default.
• W1564746483 cites W2014899456 @default.
• W1564746483 cites W2016341941 @default.
• W1564746483 cites W2019505679 @default.
• W1564746483 cites W2025192214 @default.
• W1564746483 cites W2028849454 @default.
• W1564746483 cites W2033797333 @default.
• W1564746483 cites W2045530479 @default.
• W1564746483 cites W2048008983 @default.
• W1564746483 cites W2052712443 @default.
• W1564746483 cites W2061577985 @default.
• W1564746483 cites W2063707906 @default.
• W1564746483 cites W2063756782 @default.
• W1564746483 cites W2064922908 @default.
• W1564746483 cites W2073540068 @default.
• W1564746483 cites W2082556380 @default.
• W1564746483 cites W2083710677 @default.
• W1564746483 cites W2083972768 @default.
• W1564746483 cites W2100393234 @default.
• W1564746483 cites W2101927529 @default.
• W1564746483 cites W2105597626 @default.
• W1564746483 cites W2107251975 @default.
• W1564746483 cites W2110736689 @default.
• W1564746483 cites W2120865735 @default.
• W1564746483 cites W2121501753 @default.
• W1564746483 cites W2123924185 @default.
• W1564746483 cites W2126682267 @default.
• W1564746483 cites W2128677681 @default.
• W1564746483 cites W2129034320 @default.
• W1564746483 cites W2130410032 @default.
• W1564746483 cites W2133465414 @default.
• W1564746483 cites W2134827380 @default.
• W1564746483 cites W2135827569 @default.
• W1564746483 cites W2136047357 @default.
• W1564746483 cites W2139343303 @default.
• W1564746483 cites W2142749323 @default.
• W1564746483 cites W2144720369 @default.
• W1564746483 cites W2147476151 @default.
• W1564746483 cites W2153387767 @default.
• W1564746483 cites W2156569937 @default.
• W1564746483 cites W2158101938 @default.
• W1564746483 cites W2158217645 @default.
• W1564746483 cites W2165718181 @default.
• W1564746483 cites W2169448756 @default.
• W1564746483 cites W4250973782 @default.
• W1564746483 doi "https://doi.org/10.1186/1471-2407-14-997" @default.
• W1564746483 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4391468" @default.
• W1564746483 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25539728" @default.
• W1564746483 hasPublicationYear "2014" @default.
• W1564746483 type Work @default.
• W1564746483 sameAs 1564746483 @default.
• W1564746483 citedByCount "77" @default.
• W1564746483 countsByYear W15647464832015 @default.
• W1564746483 countsByYear W15647464832016 @default.
• W1564746483 countsByYear W15647464832017 @default.
• W1564746483 countsByYear W15647464832018 @default.
• W1564746483 countsByYear W15647464832019 @default.
• W1564746483 countsByYear W15647464832020 @default.
• W1564746483 countsByYear W15647464832021 @default.
• W1564746483 countsByYear W15647464832022 @default.
• W1564746483 countsByYear W15647464832023 @default.
• W1564746483 crossrefType "journal-article" @default.
• W1564746483 hasAuthorship W1564746483A5011130785 @default.
• W1564746483 hasAuthorship W1564746483A5040411148 @default.
• W1564746483 hasAuthorship W1564746483A5045340664 @default.
• W1564746483 hasAuthorship W1564746483A5046131249 @default.
• W1564746483 hasAuthorship W1564746483A5060957121 @default.
• W1564746483 hasAuthorship W1564746483A5071830667 @default.
• W1564746483 hasAuthorship W1564746483A5084077383 @default.
• W1564746483 hasBestOaLocation W15647464831 @default.
• W1564746483 hasConcept C104317684 @default.
• W1564746483 hasConcept C127561419 @default.
• W1564746483 hasConcept C134018914 @default.

• next