Hepatic nuclear factor-1A (HNF1A) antisense long non-coding RNA subcellular location and function
Notice bibliographique
Résumé
The human and mouse hepatocyte nuclear factor 1 homeobox A (HNF1A) gene locus expresses the HNF1A transcript and a long non-coding RNA in the antisense (HNF1A-AS1) direction. HNF1A-AS1 is expressed in numerous types of cancers. Poor clinical outcomes such as higher mortality rates, greater metastatic capacity, and poor prognosis of the disease are associated with this expression. It is also involved in metabolic disorders such as fatty liver disease. Since HNF1A-AS1 is mostly localized to the nucleus, it is thought to interfere with gene expression. We studied the expression level and localization of HNF1A-AS1 RNA, HNF1A RNA, and HNF1A protein in both cancer cells and pancreatic beta cells (insulin-secreting cells of the Islets of Langerhans). We also investigated the association of HNF1A-AS1 with polycomb repressive complex 2 (PRC2). A total of four human colon cancer cell lines, including HT-29, HTC116, RKO, SW480, and a normal colon cell line CCD841 along with a lung cancer cell line A549 were cultured. Additionally, we used Min6 cells, a clonal cell line of pancreatic beta cells. Western Blot was done on all samples to quantify HNF1A protein level. RT-qPCR was done to illustrate the expression level of HNF1A-AS1 and HNF1A genes in total cell lysates as well as subcellular compartments. We used triplex domain finder (TDF) for investigating the probability of triplex formation between HNF1A-AS and DNA as well as predicting DNA binding domains of HNF1A-AS along with possible target genes. We have done RNA immunoprecipitation (RIP) to investigate the association of enhancer of zeste homolog 2 (EZH2) as a member of PRC2 complex and HNF1A-AS1. Then anchorage-independent growth assay was done to investigate the effect of inhibiting EZH2 on colony formation in HT-29 and RKO cell lines. Subcellular localization of HNF1A-AS1 varied in different cell types. In adenocarcinomic human alveolar basal epithelial cells (A549), it was localized chiefly in the cytoplasm, while in colorectal adenocarcinoma cells (HT-29) as well as Min6 cells mainly were localized in the nucleus. HNF1A protein was mostly located in the nuclear compartment, while HNF1A RNA was commonly cytoplasmic. Using TDF, we found that HNF1A-AS1 had potential to form a RNA:DNA:DNA triplex with many genomic sites. We showed the association of HNF1A-AS1 with PRC2 complex and the effect of inhibiting EZH2 on colony formation. Possible function of HNF1A-AS1 might be through forming triplex with genomic sites and recruiting EZH2 to the site. This knowledge about the location and the mechanism will increase insight for planning subsequent experimental investigations and hopefully better preventive and therapeutic modalities and consequently improve clinical outcomes in the future.
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) | 0,004 | 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 ».