Abstract 2023: Potential importance of micro-RNA-193b in human head and neck squamous cell carcinoma
Notice bibliographique
Résumé
Abstract INTRODUCTION Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide, half of these patients presenting with locally advanced disease, which despite aggressive multi-modality treatments, achieves five-year survival rates of only 50%, underscoring a need to better understand the biological bases of this disease. One approach would be examining HNSCC through the lens of micro-RNAs (miRs), which are endogenous non-coding RNAs that could post-transcriptionally regulate up to 1/3 of all human genes. EXPERIMENTAL DESIGN Global miR profilings were conducted on 54 primary human HNSCC samples, and three HNSCC cell lines (FaDu, UTSCC42a, UTSCC8), compared to normal laryngeal tissues, and a normal oral epithelial cell line, using the Taqman Low-Density Array (Applied Biosystems). The most deregulated miRs were then selected for further evaluation by knocking down the over-expressed miRs using LNAs (locked nucleic acids), and cellular effects were then determined using MTS, clonogenic, and flow cytometry assays. Micro-RNA-193b was selected for more detailed examination; mRNA candidate targets were determined by combining three different approaches described below. Binding of miR-193b with candidate mRNA was determined using a luciferase assay after co-transfection of a luciferase vector containing the 3′UTR of the mRNA target, with LNA miR-193b. RESULTS Based on the predictive power (relapse vs. non-relapse) from the clinical samples, and biological relevance in cell line studies (tumour vs. normal), six top dysregulated (over-expressed) miRs; miR-15b, miR-106b, miR-130a, miR-193b, miR-205, and miR-423, were selected for further evaluation. Only miR-106b, miR-193b and miR-205 were able to reduce cell proliferation in all three cell lines after LNA, assessed using both the MTS and clonogenic assays, with miR-193b also increasing the proportion of cells in the sub-G1 phase of the cell cycle. Candidate mRNA targets of miR-193b were elucidated by integrating in silico prediction algorithms with in vitro experimental mRNA expression profilings, and publically-available clinical mRNA expression data. A set of 11 potential mRNA targets of miR-193b were selected; 6 of which were over-expressed after miR-193b LNA knockdown. One target, Neurofibromatosis 1 (NF1), was demonstrated to directly interact with miR-193b using the luciferase vector carrying the 3′UTR of NF1. CONCLUSION Global miR profiling of HNSCC tissues and cell lines, demonstrated a trend toward over-expressed miRs. MiR-193b appears to be an important over-expressed miR in HNSCC, which targets NF1, a RAS-GTPase which hydrolyzes active RAS-GTP into inactive RAS-GDP. This failure to inactivate RAS might therefore be a potential mechanism by which several downstream oncogenic pathways of MAPK, STAT, and PI(3)K are activated, signaling continued cellular proliferation, and anti-apoptosis, hallmarks of aggressive HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2023.
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 ».