A244 ROLE OF THE NUCLEAR RECEPTOR HNF4α AND ITS MANY ISOFORMS IN COLORECTAL CANCER
Notice bibliographique
Résumé
Hepatocyte nuclear factor 4 alpha (HNF4α) is a transcription factor regulating the expression of intestinal epithelial genes. Up to 12 HNF4α isoforms can be produced by the use of promoters P1 and P2, and alternative splicing. HNF4α has recently been associated with colorectal cancer, and the variable expression of the P1 and P2 classes could explain the contradictory roles of HNF4α in this disease. However, little is known on the specific functions for each HNF4α isoform during colorectal cancer. The overall aim of this study was to elucidate how HNF4α, through the expression of its many isoforms in the colon, may contribute to the progression of colorectal cancer. More specifically, the twelve HNF4α isoforms were functionally characterized by evaluating their DNA binding and transactivation capabilities, and identifying distinct protein interaction networks using quantitative proteomics. Expression of the HNF4α isoforms was evaluated by RT-PCR in different cell lines and in different human gastrointestinal tissues. Stable cell lines expressing each of the twelve isoforms tagged with either GFP or BioID2 proteins were generated in the HCT116 human colorectal cancer cell line. EMSA, luciferase and qPCR assays were performed to characterize every single isoform. Protein interaction networks for specific isoforms expressed in the colon were characterized by quantitative mass spectrometry. Important variations in the expression of HNF4α isoforms were first observed by RT-PCR in different colorectal cancer cell lines as well as in several healthy human gastrointestinal tissues. Stable HCT116 cell lines expressing each of the HNF4α isoforms in an inducible manner were generated. Although each isoform was expressed and localized in the nucleus with a similar pattern, EMSA assays revealed differences in DNA binding capabilities for a subset of isoforms. This correlated with differences observed in the transactivation potential of these isoforms, as determined by luciferase assays and qPCR. Finally, important variations in the protein interactomes for these different isoforms were detected by quantitative mass spectrometry. The nature of these differences was related to proteins involved in transcription and chromatin assembly regulation. Our data identified differential transcriptional properties among the various HNF4α isoforms. Specific transcriptional partners were identified to differently interact with these isoforms. It is expected that the future characterization of these specific interactions will provide insight as to why HNF4α could have both oncogenic and tumor suppressive properties during colorectal cancer. CIHRNSERC
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) | 0,001 | 0,000 |
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 ».