Abstract 3418: Regulation of Dicer expression by Sox4 and its role in melanoma cell invasion and patient survival
Notice bibliographique
Résumé
Abstract Deregulated expression of Sox4 transcription factor has been observed in various types of cancers. We previously reported reduced expression of Sox4 in metastatic melanoma and its role in suppression of cell migration and invasion. We also demonstrated binding of Sox4 to the promoter sequence of Dicer, an RNase involved in maturation of miRNAs. Interestingly, altered expression of Dicer has also been reported in different types of cancers. However, the potential mechanisms which regulate Dicer expression and its potential significance in melanoma are unknown. Here we studied the regulation of Dicer expression by Sox4 and its role in suppression of melanoma invasion. Our data revealed a reduced expression of Dicer mRNA and protein upon Sox4 knockdown. On the other hand, overexpression of Sox4 increased Dicer expression at both mRNA and protein levels. We found that knockdown of Dicer, similar to Sox4 knockdown, enhances the matrigel invasion ability of melanoma cells by at least 2-fold. However, cell growth assays showed that Dicer knockdown does not have a major effect on the growth rate of melanoma cells. In addition, we revealed that overexpression of exogenous Dicer can abrogated the enhanced melanoma cells invasion upon Sox4 knockdown. Furthermore, we examined the expression of Dicer protein in different stages of melanocytic lesions by tissue microarray (TMA) and immunohistochemistry using a construct containing 30 normal nevi, 87 dysplastic nevi, 262 primary and 135 metastatic melanomas. Our data revealed that Dicer expression is inversely correlated with melanoma progression (P<0.0001). Accordingly, the number of samples with positive staining for Dicer reduced from 100% in normal nevi to 85% in dysplastic nevi and 87% in primary melanoma and further reduced to 65% in metastatic melanoma. Expression of Dicer was also negatively correlated with the American Joint Committee on Cancer (AJCC) staging of the melanoma samples (P=0.0004). Strikingly, reduced Dicer expression was correlated with a poorer overall and disease-specific 5-year survival of patients (P=0.015 and 0.0029, respectively). Multivariate Cox regression analysis revealed that reduced Dicer expression is an independent prognostic factor to predict patient outcome (P=0.030). In addition, we analyzed the possible correlation between the expression of Sox4 and Dicer in melanoma TMA samples and found a significant correlation between expression of these markers (P=0.009), further indicating the regulation of Dicer expression by Sox4. Our results pinpoint the regulation of Dicer expression by Sox4 and the critical role of Dicer and probably the miRNA machinery in the suppression of melanoma metastasis. Our data also suggest that Dicer might be a suitable marker for the prognosis of melanoma patients and a potential therapeutic target for human melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3418. doi:1538-7445.AM2012-3418
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 ».