Expressions of HuR, Methyl-HuR and Phospho-HuR in Endometrial Endometrioid Adenocarcinoma Are Associated with Clinical Features.

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Date publication

janvier 2024

Journal

International journal of molecular sciences

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GAUCHOTTE Guillaume, Dr BATTAGLIA-HSU Shyue-Fang


Tous les auteurs :
Hotton J, Gauchotte G, Mougel R, Migliorini M, Lacomme S, Battaglia-Hsu SF, Agopiantz M

Résumé

HuR regulates cytoplasmic mRNA stability and translatability, with its expression correlating with adverse outcomes in various cancers. This study aimed to assess the prognostic value and pro-oncogenic properties of HuR and its post-translational isoforms methyl-HuR and phospho-HuR in endometrial adenocarcinoma. Examining 89 endometrioid adenocarcinomas, we analyzed the relationship between HuR nuclear or cytoplasmic immunostaining, tumor-cell proliferation, and patient survival. HuR cytoplasmic expression was significantly increased in grade 3 vs. grade 1 adenocarcinomas ( < 0.001), correlating with worse overall survival (OS) ( = 0.02). Methyl-HuR cytoplasmic expression significantly decreased in grade 3 vs. grade 1 adenocarcinomas ( < 0.001) and correlated with better OS ( = 0.002). Phospho-HuR nuclear expression significantly decreased in grade 3 vs. grade 1 adenocarcinomas ( < 0.001) and non-significantly correlated with increased OS ( = 0.06). Cytoplasmic HuR expression strongly correlated with proliferation markers MCM6 (rho = 0.59 and < 0.001) and Ki67 (rho = 0.49 and < 0.001). Conversely, these latter inversely correlated with cytoplasmic methyl-HuR and nuclear phospho-HuR. Cytoplasmic HuR expression is a poor prognosis marker in endometrioid endometrial adenocarcinoma, while cytoplasmic methyl-HuR and nuclear phosphoHuR expressions are markers of better prognosis. This study highlights HuR as a promising potential therapeutic target, especially in treatment-resistant tumors, though further research is needed to understand the mechanisms regulating HuR subcellular localization and post-translational modifications.

Mots clés

HuR, cancer, endometrial adenocarcinoma, endometrium, immunohistochemistry, methyl-HuR, phospho-HuR

Référence

Int J Mol Sci. 2024 01 12;25(2):