FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385877669> ?p ?o ?g. }

• W4385877669 endingPage "4126" @default.
• W4385877669 startingPage "4126" @default.
• W4385877669 abstract "Background and Aims: Menin is a nuclear scaffold protein that regulates gene transcription in an oftentimes tissue-specific manner. Our previous work showed that menin is over-expressed in colorectal cancer (CRC); however, the full spectrum of menin function in colonic neoplasia remains unclear. Herein, we aimed to uncover novel menin-regulated pathways important for colorectal carcinogenesis. Methods: RNA-Seq analysis identified that menin regulates LXR-target gene expressions in CRC cell lines. Isolated colonic epithelium from Men1f/f;Vil1-Cre and Men1f/f mice was used to validate the results in vivo. Cholesterol content was quantified via an enzymatic assay. Results: RNA-Seq analysis in the HT-29 CRC cell line identified that menin inhibition upregulated LXR-target genes, specifically ABCG1 and ABCA1, with protein products that promote cellular cholesterol efflux. Similar results were noted across other CRC cell lines and with different methods of menin inhibition. Consistent with ABCG1 and ABCA1 upregulation, and similarly to LXR agonists, menin inhibition reduced the total cellular cholesterol in both HT-29 and HCT-15 cells. To confirm the effects of menin inhibition in vivo, we assessed Men1f/f;Vil1-Cre mice lacking menin expression in the colonic epithelium. Men1f/f;Vil1-Cre mice were found to have no distinct baseline phenotype compared to control Men1f/f mice. However, similarly to CRC cell lines, Men1f/f;Vil1-Cre mice showed an upregulation of Abcg1 and a reduction in total cellular cholesterol. Promoting cholesterol efflux, either via menin inhibition or LXR activation, was found to synergistically suppress CRC cell growth under cholesterol-depleted conditions and when administered concomitantly with small molecule EGFR inhibitors. Conclusions: Menin represses the transcription of LXR-target genes, including ABCA1 and ABCG1 in the colonic epithelium and CRC. Menin inhibition conversely upregulates LXR-target genes and reduces total cellular cholesterol, demonstrating that menin inhibition may be an important mechanism for targeting cholesterol-dependent pathways in colorectal carcinogenesis." @default.
• W4385877669 created "2023-08-17" @default.
• W4385877669 creator A5003135868 @default.
• W4385877669 creator A5006734371 @default.
• W4385877669 creator A5007157420 @default.
• W4385877669 creator A5011609263 @default.
• W4385877669 creator A5021934537 @default.
• W4385877669 creator A5030439932 @default.
• W4385877669 creator A5030473640 @default.
• W4385877669 creator A5035166264 @default.
• W4385877669 creator A5037201534 @default.
• W4385877669 creator A5042301315 @default.
• W4385877669 creator A5071041395 @default.
• W4385877669 creator A5076001179 @default.
• W4385877669 creator A5092415624 @default.
• W4385877669 creator A5092649612 @default.
• W4385877669 creator A5092649613 @default.
• W4385877669 date "2023-08-16" @default.
• W4385877669 modified "2023-10-01" @default.
• W4385877669 title "Menin Maintains Cholesterol Content in Colorectal Cancer via Repression of LXR-Mediated Transcription" @default.
• W4385877669 cites W1934924833 @default.
• W4385877669 cites W1969521020 @default.
• W4385877669 cites W1987170068 @default.
• W4385877669 cites W1991559588 @default.
• W4385877669 cites W2011910303 @default.
• W4385877669 cites W2038896680 @default.
• W4385877669 cites W2046658442 @default.
• W4385877669 cites W2049999589 @default.
• W4385877669 cites W2055296531 @default.
• W4385877669 cites W2066677392 @default.
• W4385877669 cites W2081832076 @default.
• W4385877669 cites W2089272118 @default.
• W4385877669 cites W2104450983 @default.
• W4385877669 cites W2105052532 @default.
• W4385877669 cites W2109041281 @default.
• W4385877669 cites W2111562236 @default.
• W4385877669 cites W2112460321 @default.
• W4385877669 cites W2151718828 @default.
• W4385877669 cites W2152488169 @default.
• W4385877669 cites W2162942974 @default.
• W4385877669 cites W2167009545 @default.
• W4385877669 cites W2179438025 @default.
• W4385877669 cites W2318531023 @default.
• W4385877669 cites W2530768869 @default.
• W4385877669 cites W2746888122 @default.
• W4385877669 cites W2757335411 @default.
• W4385877669 cites W2766659392 @default.
• W4385877669 cites W2768107738 @default.
• W4385877669 cites W2921841230 @default.
• W4385877669 cites W2944427239 @default.
• W4385877669 cites W2949583997 @default.
• W4385877669 cites W2982686049 @default.
• W4385877669 cites W3009963727 @default.
• W4385877669 cites W3082381233 @default.
• W4385877669 cites W3103972666 @default.
• W4385877669 cites W3130816247 @default.
• W4385877669 cites W3139427782 @default.
• W4385877669 cites W4232866872 @default.
• W4385877669 cites W4281743114 @default.
• W4385877669 doi "https://doi.org/10.3390/cancers15164126" @default.
• W4385877669 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37627154" @default.
• W4385877669 hasPublicationYear "2023" @default.
• W4385877669 type Work @default.
• W4385877669 citedByCount "0" @default.
• W4385877669 crossrefType "journal-article" @default.
• W4385877669 hasAuthorship W4385877669A5003135868 @default.
• W4385877669 hasAuthorship W4385877669A5006734371 @default.
• W4385877669 hasAuthorship W4385877669A5007157420 @default.
• W4385877669 hasAuthorship W4385877669A5011609263 @default.
• W4385877669 hasAuthorship W4385877669A5021934537 @default.
• W4385877669 hasAuthorship W4385877669A5030439932 @default.
• W4385877669 hasAuthorship W4385877669A5030473640 @default.
• W4385877669 hasAuthorship W4385877669A5035166264 @default.
• W4385877669 hasAuthorship W4385877669A5037201534 @default.
• W4385877669 hasAuthorship W4385877669A5042301315 @default.
• W4385877669 hasAuthorship W4385877669A5071041395 @default.
• W4385877669 hasAuthorship W4385877669A5076001179 @default.
• W4385877669 hasAuthorship W4385877669A5092415624 @default.
• W4385877669 hasAuthorship W4385877669A5092649612 @default.
• W4385877669 hasAuthorship W4385877669A5092649613 @default.
• W4385877669 hasBestOaLocation W43858776691 @default.
• W4385877669 hasConcept C104317684 @default.
• W4385877669 hasConcept C121608353 @default.
• W4385877669 hasConcept C127561419 @default.
• W4385877669 hasConcept C149011108 @default.
• W4385877669 hasConcept C166703698 @default.
• W4385877669 hasConcept C167400880 @default.
• W4385877669 hasConcept C185592680 @default.
• W4385877669 hasConcept C2776330080 @default.
• W4385877669 hasConcept C2777704780 @default.
• W4385877669 hasConcept C502942594 @default.
• W4385877669 hasConcept C526805850 @default.
• W4385877669 hasConcept C54355233 @default.
• W4385877669 hasConcept C555283112 @default.
• W4385877669 hasConcept C63932345 @default.
• W4385877669 hasConcept C67705224 @default.
• W4385877669 hasConcept C81885089 @default.
• W4385877669 hasConcept C86339819 @default.

• next