Abstract 4320: Investigating the role of the RNA-binding protein DEAD box ATPase 55 (DDX55) in castration resistant prostate cancer
Notice bibliographique
Résumé
Abstract Prostate cancer (PCA) is the second most frequent cancer diagnosis made in men with a global death rate of 0.4 million every year. Most PCA development requires the activity of androgen receptor (AR) activity, which required the binding of androgen. Therefore, a significant number of patients receive androgen deprivation therapy (ADT) that reduces the level of androgens, leading to a reduction in cancer growth. However, due to selective pressure, the treated PCA can relapse and become castration-resistant prostate cancer (CRPC) which is androgen-independent and highly invasive and metastatic. An urgent need for research to identify standard biomarkers and therapeutic targets are required to better manage CRPC. DEAD-box helicases are highly conserved, multifunctional proteins, many of which play a role in promoting cancer progression. However, their involvement in prostate cancer progression remains largely unexplored. DDX55, a recently discovered DEAD-box helicase, has not yet been studied in the context of prostate cancer, and its function remains uncharacterized. Our preliminary data suggests that DDX55 protein is more highly expressed in castration-resistant prostate cancer (CRPC) compared to hormone-naïve prostate cancer (HNPC). Gene expression studies using next-generation RNA sequencing revealed that silencing DDX55 reduces the expression of several AR downstream target genes, without affecting AR mRNA expression or protein levels. By further analysis, we confirmed that DDX55 silencing reduced the activity of AR, and re-expression of a DDX55 plasmid restored AR activity in DDX55 silenced cancer cells. By co-immunoreaction and mass spectrometry, we found DDX55 is complex with AR and AR coregulator and histone acetylase CBP. We observed silencing of DDX55 reduced epigenetic H3K27ac mark required for open chromatin conformation. Additionally, re-expression of a DDX55 plasmid in DDX55 silenced cells restored AR activity and H3K27ac. We propose that DDX55 regulates CBP for H3K27ac to induce chromatin accessibility for the expression of AR downstream target genes. To further understand this, we conducted pilot animal experiments, and found that DDX55 is a regulator of PCA progression. Our project will characterize DDX55 in prostate cancer by analysing its expression in a large repertoire of cancer specimens to determine its potential as a diagnostic marker, investigate the molecular mechanism through which DDX55 regulates AR activation, with the goal of identifying new therapeutic targets for prostate cancer, and develop an animal model to study the role of DDX55 in cancer progression to study its involvement in vivo invasion and metastasis. This research is expected to advance our understanding of the mechanisms of prostate cancer progression and help identify ways to target it for improved management of the disease. Citation Format: Ziwei (Mia) Cai, Syam Somasekharan. Investigating the role of the RNA-binding protein DEAD box ATPase 55 (DDX55) in castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4320.
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) | 0,002 | 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 ».