Matches in SemOpenAlex for { <https://semopenalex.org/work/W1535752778> ?p ?o ?g. }
- W1535752778 endingPage "15558" @default.
- W1535752778 startingPage "15549" @default.
- W1535752778 abstract "Non-thyroidal illness syndrome (NTIS), characterized by low serum 3,5,3′-triiodothyronine (T3) with normal l-thyroxine (T4) levels, is associated with malignancy. Decreased activity of type I 5′-deiodinase (DIO1), which converts T4 to T3, contributes to NTIS. T3 binds to thyroid hormone receptor, which heterodimerizes with retinoid X receptor (RXR) and regulates transcription of target genes, such as DIO1. NF-κB activation by inflammatory cytokines inhibits DIO1 expression. The oncogene astrocyte elevated gene-1 (AEG-1) inhibits RXR-dependent transcription and activates NF-κB. Here, we interrogated the role of AEG-1 in NTIS in the context of hepatocellular carcinoma (HCC). T3-mediated gene regulation was analyzed in human HCC cells, with overexpression or knockdown of AEG-1, and primary hepatocytes from AEG-1 transgenic (Alb/AEG-1) and AEG-1 knock-out (AEG-1KO) mice. Serum T3 and T4 levels were checked in Alb/AEG-1 mice and human HCC patients. AEG-1 and DIO1 levels in human HCC samples were analyzed by immunohistochemistry. AEG-1 inhibited T3-mediated gene regulation in human HCC cells and mouse hepatocytes. AEG-1 overexpression repressed and AEG-1 knockdown induced DIO1 expression. An inverse correlation was observed between AEG-1 and DIO1 levels in human HCC patients. Low T3 with normal T4 was observed in the sera of HCC patients and Alb/AEG-1 mice. Inhibition of co-activator recruitment to RXR and activation of NF-κB were identified to play a role in AEG-1-mediated down-regulation of DIO1. AEG-1 thus might play a role in NTIS associated with HCC and other cancers.Background:Astrocyte elevated gene-1 (AEG-1) inhibits retinoid X receptor (RXR) function and is overexpressed in human hepatocellular carcinoma (HCC), which is associated with non-thyroidal illness syndrome (NTIS).Results:AEG-1 inhibits thyroid hormone (T3) function by down-regulating type I 5′-deiodinase (DIO1) thus contributing to NTIS.Conclusion:A novel role of AEG-1 is identified regulating cancer-associated NTIS.Significance:AEG-1 inhibition might alleviate cancer-associated debilitating disorders. Non-thyroidal illness syndrome (NTIS), characterized by low serum 3,5,3′-triiodothyronine (T3) with normal l-thyroxine (T4) levels, is associated with malignancy. Decreased activity of type I 5′-deiodinase (DIO1), which converts T4 to T3, contributes to NTIS. T3 binds to thyroid hormone receptor, which heterodimerizes with retinoid X receptor (RXR) and regulates transcription of target genes, such as DIO1. NF-κB activation by inflammatory cytokines inhibits DIO1 expression. The oncogene astrocyte elevated gene-1 (AEG-1) inhibits RXR-dependent transcription and activates NF-κB. Here, we interrogated the role of AEG-1 in NTIS in the context of hepatocellular carcinoma (HCC). T3-mediated gene regulation was analyzed in human HCC cells, with overexpression or knockdown of AEG-1, and primary hepatocytes from AEG-1 transgenic (Alb/AEG-1) and AEG-1 knock-out (AEG-1KO) mice. Serum T3 and T4 levels were checked in Alb/AEG-1 mice and human HCC patients. AEG-1 and DIO1 levels in human HCC samples were analyzed by immunohistochemistry. AEG-1 inhibited T3-mediated gene regulation in human HCC cells and mouse hepatocytes. AEG-1 overexpression repressed and AEG-1 knockdown induced DIO1 expression. An inverse correlation was observed between AEG-1 and DIO1 levels in human HCC patients. Low T3 with normal T4 was observed in the sera of HCC patients and Alb/AEG-1 mice. Inhibition of co-activator recruitment to RXR and activation of NF-κB were identified to play a role in AEG-1-mediated down-regulation of DIO1. AEG-1 thus might play a role in NTIS associated with HCC and other cancers. Astrocyte elevated gene-1 (AEG-1) inhibits retinoid X receptor (RXR) function and is overexpressed in human hepatocellular carcinoma (HCC), which is associated with non-thyroidal illness syndrome (NTIS). AEG-1 inhibits thyroid hormone (T3) function by down-regulating type I 5′-deiodinase (DIO1) thus contributing to NTIS. A novel role of AEG-1 is identified regulating cancer-associated NTIS." @default.
- W1535752778 created "2016-06-24" @default.
- W1535752778 creator A5009062868 @default.
- W1535752778 creator A5013378385 @default.
- W1535752778 creator A5014030486 @default.
- W1535752778 creator A5022501910 @default.
- W1535752778 creator A5027901109 @default.
- W1535752778 creator A5031490587 @default.
- W1535752778 creator A5060723568 @default.
- W1535752778 creator A5064623175 @default.
- W1535752778 creator A5076202183 @default.
- W1535752778 creator A5087009545 @default.
- W1535752778 creator A5091194969 @default.
- W1535752778 date "2015-06-01" @default.
- W1535752778 modified "2023-10-15" @default.
- W1535752778 title "Astrocyte Elevated Gene-1 (AEG-1) Contributes to Non-thyroidal Illness Syndrome (NTIS) Associated with Hepatocellular Carcinoma (HCC)" @default.
- W1535752778 cites W1501286679 @default.
- W1535752778 cites W1533021978 @default.
- W1535752778 cites W156511211 @default.
- W1535752778 cites W1826361194 @default.
- W1535752778 cites W1886282467 @default.
- W1535752778 cites W1966970787 @default.
- W1535752778 cites W1973015093 @default.
- W1535752778 cites W1988990159 @default.
- W1535752778 cites W1993080614 @default.
- W1535752778 cites W1996180467 @default.
- W1535752778 cites W2001519284 @default.
- W1535752778 cites W2001699369 @default.
- W1535752778 cites W2015745874 @default.
- W1535752778 cites W2020680441 @default.
- W1535752778 cites W2021932599 @default.
- W1535752778 cites W2026147554 @default.
- W1535752778 cites W2032303618 @default.
- W1535752778 cites W2042388934 @default.
- W1535752778 cites W2058148459 @default.
- W1535752778 cites W2058303237 @default.
- W1535752778 cites W2074261333 @default.
- W1535752778 cites W2079745451 @default.
- W1535752778 cites W2089774164 @default.
- W1535752778 cites W2091544680 @default.
- W1535752778 cites W2103446563 @default.
- W1535752778 cites W2109458276 @default.
- W1535752778 cites W2117342171 @default.
- W1535752778 cites W2141375310 @default.
- W1535752778 cites W2150046477 @default.
- W1535752778 cites W2155122828 @default.
- W1535752778 cites W2159297057 @default.
- W1535752778 cites W2164798159 @default.
- W1535752778 cites W2168760648 @default.
- W1535752778 doi "https://doi.org/10.1074/jbc.m115.649707" @default.
- W1535752778 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4505468" @default.
- W1535752778 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25944909" @default.
- W1535752778 hasPublicationYear "2015" @default.
- W1535752778 type Work @default.
- W1535752778 sameAs 1535752778 @default.
- W1535752778 citedByCount "20" @default.
- W1535752778 countsByYear W15357527782015 @default.
- W1535752778 countsByYear W15357527782016 @default.
- W1535752778 countsByYear W15357527782017 @default.
- W1535752778 countsByYear W15357527782018 @default.
- W1535752778 countsByYear W15357527782019 @default.
- W1535752778 countsByYear W15357527782020 @default.
- W1535752778 countsByYear W15357527782021 @default.
- W1535752778 countsByYear W15357527782022 @default.
- W1535752778 countsByYear W15357527782023 @default.
- W1535752778 crossrefType "journal-article" @default.
- W1535752778 hasAuthorship W1535752778A5009062868 @default.
- W1535752778 hasAuthorship W1535752778A5013378385 @default.
- W1535752778 hasAuthorship W1535752778A5014030486 @default.
- W1535752778 hasAuthorship W1535752778A5022501910 @default.
- W1535752778 hasAuthorship W1535752778A5027901109 @default.
- W1535752778 hasAuthorship W1535752778A5031490587 @default.
- W1535752778 hasAuthorship W1535752778A5060723568 @default.
- W1535752778 hasAuthorship W1535752778A5064623175 @default.
- W1535752778 hasAuthorship W1535752778A5076202183 @default.
- W1535752778 hasAuthorship W1535752778A5087009545 @default.
- W1535752778 hasAuthorship W1535752778A5091194969 @default.
- W1535752778 hasBestOaLocation W15357527781 @default.
- W1535752778 hasConcept C109115496 @default.
- W1535752778 hasConcept C121608353 @default.
- W1535752778 hasConcept C126322002 @default.
- W1535752778 hasConcept C134018914 @default.
- W1535752778 hasConcept C173396325 @default.
- W1535752778 hasConcept C2777542381 @default.
- W1535752778 hasConcept C2778019345 @default.
- W1535752778 hasConcept C2781018059 @default.
- W1535752778 hasConcept C2781057625 @default.
- W1535752778 hasConcept C29537977 @default.
- W1535752778 hasConcept C502942594 @default.
- W1535752778 hasConcept C526584372 @default.
- W1535752778 hasConcept C529278444 @default.
- W1535752778 hasConcept C54355233 @default.
- W1535752778 hasConcept C71924100 @default.
- W1535752778 hasConcept C81885089 @default.
- W1535752778 hasConcept C86803240 @default.
- W1535752778 hasConceptScore W1535752778C109115496 @default.
- W1535752778 hasConceptScore W1535752778C121608353 @default.
- W1535752778 hasConceptScore W1535752778C126322002 @default.