FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308169944> ?p ?o ?g. }

• W4308169944 abstract "Ovarian cancer (OC) is characterized by a low response rate and high frequency of resistance development to currently available treatments. The therapeutic potential of histone methyltransferase DOT1L inhibitor in OC cells has been demonstrated, but optimal efficacy and safety of this targeted therapy approach still require improvement. We set forth to evaluate if this problem can be overcome by combinatorial targeting of this epigenetic modifier and menin, one of its functional partners in chromatin.siRNA-mediated gene knock-down and pharmacological inhibition of menin, a key component of the MLL/SET1 complex and a fitness gene in OC cells, coupled to cell proliferation assays on a panel of high grade serous OC cell lines, including chemotherapy-sensitive and -resistant clones, were applied in order to evaluate how depletion or blockade of this enzyme influences growth and viability of OC cells. RNA sequencing was applied to identify menin target genes and pathways, and the effects of combined inhibition of menin and DOT1L on growth and transcriptome of these OC models were evaluated.Silencing and pharmacological inhibition of menin exert antiproliferative effects in all OC cells tested and, in PEO1 and PEO4 cells, a profound impact on transcriptome via down-regulation of cell cycle regulatory pathways, aryl hydrocarbon receptor, MYC and KRAS signalling. We demonstrated association of menin and DOT1L in OC cells and identified a subset of genes co-regulated by the two factors. Interestingly, co-treatment with DOT1L and menin pharmacological inhibitors exerts an additive effect on growth inhibition on chemotherapy-sensitive and -refractory OC cells mediated by transcriptome changes controlled by menin and DOT1L activities.These results indicate that menin functionally cooperates with DOT1L in OC cells modulating transcription of genes involved in key cellular functions including, among others, cell proliferation and survival, that are strongly affected by combined inhibition of these two epigenetic regulators, suggesting that this may represent a novel therapeutic strategy for chemotherapy-resistant OCs.NA; The manuscript does not contain clinical trials." @default.
• W4308169944 created "2022-11-08" @default.
• W4308169944 creator A5009028518 @default.
• W4308169944 creator A5010950670 @default.
• W4308169944 creator A5014443634 @default.
• W4308169944 creator A5024644508 @default.
• W4308169944 creator A5035591964 @default.
• W4308169944 creator A5050045829 @default.
• W4308169944 creator A5061245348 @default.
• W4308169944 creator A5076437454 @default.
• W4308169944 creator A5076810301 @default.
• W4308169944 creator A5085978275 @default.
• W4308169944 date "2022-11-04" @default.
• W4308169944 modified "2023-09-26" @default.
• W4308169944 title "Combinatorial targeting of menin and the histone methyltransferase DOT1L as a novel therapeutic strategy for treatment of chemotherapy-resistant ovarian cancer" @default.
• W4308169944 cites W1781764024 @default.
• W4308169944 cites W1839238574 @default.
• W4308169944 cites W1981695027 @default.
• W4308169944 cites W2017446931 @default.
• W4308169944 cites W2036897871 @default.
• W4308169944 cites W2055296531 @default.
• W4308169944 cites W2075711878 @default.
• W4308169944 cites W2096086497 @default.
• W4308169944 cites W2107519216 @default.
• W4308169944 cites W2123696077 @default.
• W4308169944 cites W2130410032 @default.
• W4308169944 cites W2137876306 @default.
• W4308169944 cites W2138207763 @default.
• W4308169944 cites W2149858927 @default.
• W4308169944 cites W2151718828 @default.
• W4308169944 cites W2154218976 @default.
• W4308169944 cites W2169456326 @default.
• W4308169944 cites W2179438025 @default.
• W4308169944 cites W2344726805 @default.
• W4308169944 cites W2428128364 @default.
• W4308169944 cites W2554624179 @default.
• W4308169944 cites W2582766566 @default.
• W4308169944 cites W2594370868 @default.
• W4308169944 cites W2596054989 @default.
• W4308169944 cites W2611381258 @default.
• W4308169944 cites W2735132087 @default.
• W4308169944 cites W2761866581 @default.
• W4308169944 cites W2769932985 @default.
• W4308169944 cites W2803375800 @default.
• W4308169944 cites W2807649309 @default.
• W4308169944 cites W2886882464 @default.
• W4308169944 cites W2915041127 @default.
• W4308169944 cites W2921058551 @default.
• W4308169944 cites W2921650138 @default.
• W4308169944 cites W2951623443 @default.
• W4308169944 cites W2985832033 @default.
• W4308169944 cites W2992263057 @default.
• W4308169944 cites W3005714839 @default.
• W4308169944 cites W3007510394 @default.
• W4308169944 cites W3033823212 @default.
• W4308169944 cites W3039604895 @default.
• W4308169944 cites W3125923658 @default.
• W4308169944 cites W3128646645 @default.
• W4308169944 cites W3167620265 @default.
• W4308169944 cites W3210225758 @default.
• W4308169944 cites W3217554630 @default.
• W4308169944 cites W4211203170 @default.
• W4308169944 cites W4223964145 @default.
• W4308169944 cites W4225413409 @default.
• W4308169944 cites W4241093998 @default.
• W4308169944 cites W4281705734 @default.
• W4308169944 cites W4285799995 @default.
• W4308169944 doi "https://doi.org/10.1186/s12935-022-02740-6" @default.
• W4308169944 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36333801" @default.
• W4308169944 hasPublicationYear "2022" @default.
• W4308169944 type Work @default.
• W4308169944 citedByCount "1" @default.
• W4308169944 countsByYear W43081699442023 @default.
• W4308169944 crossrefType "journal-article" @default.
• W4308169944 hasAuthorship W4308169944A5009028518 @default.
• W4308169944 hasAuthorship W4308169944A5010950670 @default.
• W4308169944 hasAuthorship W4308169944A5014443634 @default.
• W4308169944 hasAuthorship W4308169944A5024644508 @default.
• W4308169944 hasAuthorship W4308169944A5035591964 @default.
• W4308169944 hasAuthorship W4308169944A5050045829 @default.
• W4308169944 hasAuthorship W4308169944A5061245348 @default.
• W4308169944 hasAuthorship W4308169944A5076437454 @default.
• W4308169944 hasAuthorship W4308169944A5076810301 @default.
• W4308169944 hasAuthorship W4308169944A5085978275 @default.
• W4308169944 hasBestOaLocation W43081699441 @default.
• W4308169944 hasConcept C104317684 @default.
• W4308169944 hasConcept C105696609 @default.
• W4308169944 hasConcept C119056186 @default.
• W4308169944 hasConcept C121608353 @default.
• W4308169944 hasConcept C150194340 @default.
• W4308169944 hasConcept C162317418 @default.
• W4308169944 hasConcept C2781187634 @default.
• W4308169944 hasConcept C29537977 @default.
• W4308169944 hasConcept C41091548 @default.
• W4308169944 hasConcept C501734568 @default.
• W4308169944 hasConcept C502942594 @default.
• W4308169944 hasConcept C54355233 @default.
• W4308169944 hasConcept C62112901 @default.
• W4308169944 hasConcept C83640560 @default.
• W4308169944 hasConcept C86803240 @default.

• next