Titre
Immune Checkpoint and Telomerase Crosstalk Is Mediated by miRNA-138 in Bladder Cancer.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
El Ahanidi, H.
Auteure/Auteur
El Azzouzi, M.
Auteure/Auteur
Hafidi Alaoui, C.
Auteure/Auteur
Tetou, M.
Auteure/Auteur
Bensaid, M.
Auteure/Auteur
Chaoui, I.
Auteure/Auteur
Benbacer, L.
Auteure/Auteur
Hassan, I.
Auteure/Auteur
Oukabli, M.
Auteure/Auteur
Michaud, K.
Auteure/Auteur
Ameur, A.
Auteure/Auteur
Al Bouzidi, A.
Auteure/Auteur
El Mzibri, M.
Auteure/Auteur
Jandus, C.
Auteure/Auteur
Attaleb, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2234-943X
Statut éditorial
Publié
Date de publication
2021
Volume
11
Première page
795242
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Tumor recurrence and progression in non-muscle invasive bladder cancer (NMIBC), therapy failure, and severe side effects in muscle invasive bladder cancer (MIBC) are the major challenges in the clinical management of bladder cancer (BC). Here, we identify new molecular targetable signatures to improve BC patients' stratification and the outcome of current immunotherapies.
In a prospective cohort of 70 BC patients, we assessed the genetic and molecular regulation of TERT in maintaining telomere length in parallel to immune checkpoint and microRNA expression.
TERT was undetectable in healthy bladder tissues but upregulated in invasive BC stages and high tumor grade. Its expression was linked with the combined effect of the C250T mutation and THOR hypermethylation, associated with progressing tumors and maintaining of telomere length. In the same cohort, PD-L1 scored highest in NMIBC, while PD-L2 was upregulated in MIBC. We also show that miR-100-5p and 138-5p were highly expressed in healthy bladder specimens and cell line, while expression decreased in the BC tissues and BC cell lines. In line with the binding prediction for these miRNAs on target genes, miRs 100-5p and 138-5p expression strongly inverse correlated with TERT, PD-L1, and PD-L2 expression, but not PD1.
We identify a loop involving TERT, PD1-ligands, and miR-138-5p in BC, that might represent not only a useful biomarker for improved diagnosis and patients' stratification but also as a promising axis that might be therapeutically targeted in situ.
In a prospective cohort of 70 BC patients, we assessed the genetic and molecular regulation of TERT in maintaining telomere length in parallel to immune checkpoint and microRNA expression.
TERT was undetectable in healthy bladder tissues but upregulated in invasive BC stages and high tumor grade. Its expression was linked with the combined effect of the C250T mutation and THOR hypermethylation, associated with progressing tumors and maintaining of telomere length. In the same cohort, PD-L1 scored highest in NMIBC, while PD-L2 was upregulated in MIBC. We also show that miR-100-5p and 138-5p were highly expressed in healthy bladder specimens and cell line, while expression decreased in the BC tissues and BC cell lines. In line with the binding prediction for these miRNAs on target genes, miRs 100-5p and 138-5p expression strongly inverse correlated with TERT, PD-L1, and PD-L2 expression, but not PD1.
We identify a loop involving TERT, PD1-ligands, and miR-138-5p in BC, that might represent not only a useful biomarker for improved diagnosis and patients' stratification but also as a promising axis that might be therapeutically targeted in situ.
PID Serval
serval:BIB_3DD67FC130B6
PMID
Open Access
Oui
Date de création
2022-03-01T12:12:00.294Z
Date de création dans IRIS
2025-05-20T19:48:52Z
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Nom
35223454.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
7.16 MB
Format
Adobe PDF
PID Serval
serval:BIB_3DD67FC130B6.P001
URN
urn:nbn:ch:serval-BIB_3DD67FC130B65
Somme de contrôle
(MD5):b9f1ad30de8423ec9194e45e70c53301