A MiR181/Sirtuin1 regulatory circuit modulates drug response in biliary cancers.
Biliary tract cancer
Biomarkers
Cancer genomics
Cancer resistance
MicroRNA
miR-181
Journal
Clinical and experimental medicine
ISSN: 1591-9528
Titre abrégé: Clin Exp Med
Pays: Italy
ID NLM: 100973405
Informations de publication
Date de publication:
10 Apr 2024
10 Apr 2024
Historique:
received:
25
01
2024
accepted:
14
03
2024
medline:
10
4
2024
pubmed:
10
4
2024
entrez:
10
4
2024
Statut:
epublish
Résumé
Despite recent advances, biliary tract cancer (BTC) remains one of the most lethal tumor worldwide due to late diagnosis, limited therapeutic strategies and resistance to conventional therapies. In recent years, high-throughput technologies have enabled extensive genome, and transcriptome sequencing unveiling, among others, the regulatory potential of microRNAs (miRNAs). Compelling evidence shown that miRNA are attractive therapeutic targets and promising candidates as biomarkers for various therapy-resistant tumors. The analysis of miRNA profile successfully identified miR-181c and -181d as significantly downregulated in BTC patients. Low miR-181c and -181d expression levels were correlated with worse prognosis and poor treatment efficacy. In fact, progression-free survival analysis indicated poor survival rates in miR-181c and -181d low expressing patients. The expression profile of miR-181c and -181d in BTC cell lines revealed that both miRNAs were dysregulated. Functional in vitro experiments in BTC cell lines showed that overexpression of miR-181c and -181d affected cell viability and increased sensitivity to chemotherapy compared to controls. In addition, by using bioinformatic tools we showed that the miR-181c/d functional role is determined by binding to their target SIRT1 (Sirtuin 1). Moreover, BTC patients expressing high levels of miR-181 and low SIRT1 shown an improved survival and treatment response. An integrative network analysis demonstrated that, miR-181/SIRT1 circuit had a regulatory effect on several important metabolic tumor-related processes. Our study demonstrated that miR-181c and -181d act as tumor suppressor miRNA in BTC, suggesting the potential use as therapeutic strategy in resistant cancers and as predictive biomarker in the precision medicine of BTC.
Identifiants
pubmed: 38598008
doi: 10.1007/s10238-024-01332-0
pii: 10.1007/s10238-024-01332-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
74Subventions
Organisme : Ministero dell'Istruzione, dell'Universita'
ID : PRIN2020 - 2020XBCMHJ
Organisme : Ministero dell'Istruzione, dell'Universita'
ID : PRIN2020 - 2020XBCMHJ
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PRIN2022 - 20227RH9M4
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PRIN2022 - 20227RH9M4
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PRIN2022 - 20227RH9M4
Organisme : Fondazione AIRC per la ricerca sul cancro ETS
ID : IG26414/2021
Organisme : Fondazione AIRC per la ricerca sul cancro ETS
ID : IG26414/2021
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 800924
Organisme : Regione Campania
ID : Genomica e Terapia
Informations de copyright
© 2024. The Author(s).
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