Matches in SemOpenAlex for { <https://semopenalex.org/work/W2022243246> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W2022243246 abstract "Evasion of apoptosis is a known feature of cancer cells. One mechanism of deregulating the apoptotic pathway is through overexpression of anti-apoptotic Bcl-2 family members. ABT-263 is a first-in-class Bcl-2 family inhibitor that restores the ability of cancer cells to undergo apoptosis. However, many cancer cells are resistant to ABT-263 due to high levels of a Bcl-2 family member Mcl-1, which is not targeted by the drug. Mcl-1 expression is known to be regulated transcriptionally, translationally, and through proteosome-mediated degradation. Recently, Mcl-1 expression was shown to be affected by microRNAs (miRNAs). In order to identify miRNAs that modulate the sensitivity of cancer cells to ABT-263, we screened a library of 810 human miRNA mimics in HCT-116 cells in the presence of ABT-263. The screen revealed 19 miRNAs that sensitize HCT-116 cells to ABT-263. Fifteen of these miRNAs were also shown to sensitize CHL1 melanoma cells to the same agent. We further evaluated twelve of the strongest sensitizers in these cell lines. We found that these sensitizers induced apoptosis only in the presence of ABT-263. In addition, while all twelve of these miRNAs reduced Mcl-1 protein expression, only ten of them targeted Mcl-1 through direct binding to the Mcl-1 3′ untranslated regions (3′-UTR) of the gene. Other resistance pathways and regulators of Mcl-1 expression may be identified using this method. Our data can be used to design miRNA replacement therapies to increase sensitivity to Bcl-2 antagonists. The expression of the 12 marker microRNAs is now being correlated to the sensitivity to ABT-263 in order to enable rational patient selection in ABT-263 clinical trials. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B4" @default.
- W2022243246 created "2016-06-24" @default.
- W2022243246 creator A5025864043 @default.
- W2022243246 creator A5033293350 @default.
- W2022243246 creator A5034213336 @default.
- W2022243246 date "2010-04-01" @default.
- W2022243246 modified "2023-09-25" @default.
- W2022243246 title "Abstract B4: A microRNA screen to identify modulators of sensitivity to Bcl-2 inhibitor ABT-263" @default.
- W2022243246 doi "https://doi.org/10.1158/1078-0432.tcme10-b4" @default.
- W2022243246 hasPublicationYear "2010" @default.
- W2022243246 type Work @default.
- W2022243246 sameAs 2022243246 @default.
- W2022243246 citedByCount "0" @default.
- W2022243246 crossrefType "proceedings-article" @default.
- W2022243246 hasAuthorship W2022243246A5025864043 @default.
- W2022243246 hasAuthorship W2022243246A5033293350 @default.
- W2022243246 hasAuthorship W2022243246A5034213336 @default.
- W2022243246 hasConcept C104317684 @default.
- W2022243246 hasConcept C105580179 @default.
- W2022243246 hasConcept C121608353 @default.
- W2022243246 hasConcept C127561419 @default.
- W2022243246 hasConcept C145059251 @default.
- W2022243246 hasConcept C153911025 @default.
- W2022243246 hasConcept C190283241 @default.
- W2022243246 hasConcept C502942594 @default.
- W2022243246 hasConcept C54355233 @default.
- W2022243246 hasConcept C81885089 @default.
- W2022243246 hasConcept C86803240 @default.
- W2022243246 hasConcept C89604277 @default.
- W2022243246 hasConcept C96232424 @default.
- W2022243246 hasConceptScore W2022243246C104317684 @default.
- W2022243246 hasConceptScore W2022243246C105580179 @default.
- W2022243246 hasConceptScore W2022243246C121608353 @default.
- W2022243246 hasConceptScore W2022243246C127561419 @default.
- W2022243246 hasConceptScore W2022243246C145059251 @default.
- W2022243246 hasConceptScore W2022243246C153911025 @default.
- W2022243246 hasConceptScore W2022243246C190283241 @default.
- W2022243246 hasConceptScore W2022243246C502942594 @default.
- W2022243246 hasConceptScore W2022243246C54355233 @default.
- W2022243246 hasConceptScore W2022243246C81885089 @default.
- W2022243246 hasConceptScore W2022243246C86803240 @default.
- W2022243246 hasConceptScore W2022243246C89604277 @default.
- W2022243246 hasConceptScore W2022243246C96232424 @default.
- W2022243246 hasLocation W20222432461 @default.
- W2022243246 hasOpenAccess W2022243246 @default.
- W2022243246 hasPrimaryLocation W20222432461 @default.
- W2022243246 hasRelatedWork W1765908803 @default.
- W2022243246 hasRelatedWork W2051928563 @default.
- W2022243246 hasRelatedWork W2089532685 @default.
- W2022243246 hasRelatedWork W2098910097 @default.
- W2022243246 hasRelatedWork W2126532140 @default.
- W2022243246 hasRelatedWork W2135774507 @default.
- W2022243246 hasRelatedWork W2144840682 @default.
- W2022243246 hasRelatedWork W2156807354 @default.
- W2022243246 hasRelatedWork W2227783113 @default.
- W2022243246 hasRelatedWork W2272744924 @default.
- W2022243246 hasRelatedWork W2620449054 @default.
- W2022243246 hasRelatedWork W2742030022 @default.
- W2022243246 hasRelatedWork W2883782670 @default.
- W2022243246 hasRelatedWork W2892395616 @default.
- W2022243246 hasRelatedWork W2996530565 @default.
- W2022243246 hasRelatedWork W3014572587 @default.
- W2022243246 hasRelatedWork W3094692908 @default.
- W2022243246 hasRelatedWork W3174277730 @default.
- W2022243246 hasRelatedWork W98526587 @default.
- W2022243246 hasRelatedWork W2241106743 @default.
- W2022243246 isParatext "false" @default.
- W2022243246 isRetracted "false" @default.
- W2022243246 magId "2022243246" @default.
- W2022243246 workType "article" @default.