Abstract PO-002: Epigenetic regulation of metabolic pathways in response of breast cancer cells to stilbenoids
Notice bibliographique
Résumé
Abstract Epigenetics is the study of heritable gene expression changes that are not due to a change in the DNA sequence. Due to the inherent reversibility of epigenetic states, epigenetic modifications, particularly DNA methylation, have attracted a significant amount of attention for the prevention and treatment of cancer. Aberrations in DNA methylation occur during cancer initiation, promotion and progression. Recent evidence suggests that these aberrations may contribute to metabolic disturbances in cancer. Although limited, there are pieces of evidence demonstrating that dietary bioactive compounds, including polyphenols from the stilbenoid subclass, such as resveratrol and pterostilbene, can modulate gene expression by targeting DNA methylation. Our recent investigation into DNA methylation patterns using Illumina 450K BeadChip microarray demonstrates that loci-specific increases and decreases in DNA methylation occur in breast cancer cells in response to resveratrol. We have identified 4,183 differentially methylated CpG sites in MCF10CA1h and 6,347 differentially methylated CpG sites in MCF10CA1a breast cancer cells upon 9-day treatment with 15µM resveratrol as compared with control cells (0.05≤differential methylation≥-0.05, nominal p<0.05, limma t-test). Interestingly, the majority of differentially methylated CpGs showed increases in DNA methylation levels after resveratrol treatment and fell into a category of regulation of oncogenic cellular signal transduction pathways. On the other hand, CpG loci hypomethylated upon resveratrol corresponded to numerous genes with tumor suppressor functions. In the present study, we extended our investigation into genes associated with metabolic pathways whose DNA methylation status changes in response of MCF10CA1a breast cancer cells to 9-day treatment with 15µM resveratrol. We found 583 CpG sites corresponding to 365 genes linked to metabolic processes. Among those genes, peroxisome proliferator-activated receptor PPARγC1A, PPARγC1B and PPARδ were hypermethylated whereas PPARα was hypomethylated. PPARs are nuclear receptors that regulate transcription of multiple genes, including targets associated with metabolic processes such as glucose homeostasis, fatty acid oxidation and synthesis. Interestingly, PPARs were shown to recruit ten-eleven translocation (TET) enzymes to specific DNA regions in order to facilitate decrease in DNA methylation and activation of transcription. This constitutes additional layer of complexity and may contribute to epigenetic effects of stilbenoids. Our results provide novel evidence on the mechanistic link between metabolism, epigenetics and stilbenoids which opens the door to further investigation on mechanistic players that could contribute to the development of epigenetic-targeting anti-cancer strategies. This study was supported by the University of British Columbia VP Academic (#10R76632) Award, CFI John R. Evans Leadership Fund and BC Knowledge Development Fund granted to B.S. Citation Format: Barbara Stefanska, Cayla Boycott, Tony Yang. Epigenetic regulation of metabolic pathways in response of breast cancer cells to stilbenoids [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-002.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».