The lncRNA 'UCA1' modulates the response ...
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Article dans une revue scientifique: Article original
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Title :
The lncRNA 'UCA1' modulates the response to chemotherapy of ovarian cancer through direct binding to miR-27a-5p and control of UBE2N levels.
Author(s) :
Wambecke, A. [Auteur]
Centre Régional de Lutte contre le Cancer François Baclesse [Caen] [UNICANCER/CRLC]
Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers [ANTICIPE]
Ahmad, M. [Auteur]
Morice, P. M. [Auteur]
Lambert, B. [Auteur]
Weiswald, L. B. [Auteur]
Vernon, M. [Auteur]
Vigneron, N. [Auteur]
Abeilard, E. [Auteur]
Brotin, E. [Auteur]
Figeac, Martin [Auteur]
Genomic @ Lille - PLBS [GO@L]
Gauduchon, P. [Auteur]
Poulain, L. [Auteur]
Denoyelle, C. [Auteur]
Meryet-Figuiere, M. [Auteur]
Centre Régional de Lutte contre le Cancer François Baclesse [Caen] [UNICANCER/CRLC]
Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers [ANTICIPE]
Ahmad, M. [Auteur]
Morice, P. M. [Auteur]
Lambert, B. [Auteur]
Weiswald, L. B. [Auteur]
Vernon, M. [Auteur]
Vigneron, N. [Auteur]
Abeilard, E. [Auteur]
Brotin, E. [Auteur]
Figeac, Martin [Auteur]
Genomic @ Lille - PLBS [GO@L]
Gauduchon, P. [Auteur]
Poulain, L. [Auteur]
Denoyelle, C. [Auteur]
Meryet-Figuiere, M. [Auteur]
Journal title :
Mol Oncol
Abbreviated title :
Mol Oncol
Volume number :
15
Pages :
p. 3659-3678
Publication date :
2021-12
ISSN :
1878-0261
English keyword(s) :
ceRNA
chemoresistance
miR-27a-5p
ovarian cancer
patient-derived organoid
lncRNA UCA1
chemoresistance
miR-27a-5p
ovarian cancer
patient-derived organoid
lncRNA UCA1
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Ovarian cancer (OC) is the leading cause of death in patients with gynecologic cancers. Due to late diagnosis and resistance to chemotherapy, the 5-year survival rate in patients with OC is below 40%. We observed that UCA1, ...
Show more >Ovarian cancer (OC) is the leading cause of death in patients with gynecologic cancers. Due to late diagnosis and resistance to chemotherapy, the 5-year survival rate in patients with OC is below 40%. We observed that UCA1, a lncRNA previously reported to play an oncogenic role in several malignancies, is overexpressed in the chemoresistant OC cell line OAW42-R compared to their chemotherapy-sensitive counterpart OAW42. Additionally, UCA1 overexpression was related to poor prognosis in two independent patient cohorts. Currently, the molecular mechanisms through which UCA1 acts in OC are poorly understood. We demonstrated that downregulation of the short isoform of UCA1 sensitized OC cells to cisplatin and that UCA1 acted as competing endogenous RNA to miR-27a-5p. Upon UCA1 downregulation, miR-27a-5p downregulated its direct target UBE2N leading to the upregulation of BIM, a proapoptotic protein of the Bcl2 family. The upregulation of BIM is the event responsible for the sensitization of OC cells to cisplatin. In order to model response to therapy in patients with OC, we used several patient-derived organoid cultures, a model faithfully mimicking patient’s response to therapy. Inhibition of UBE2N sensitized patient-derived organoids to platinum salts. In conclusion, response to treatment in patients with OC is regulated by the UCA1/miR-27a-5p/UBE2N axis, where UBE2N inhibition could potentially represent a novel therapeutic strategy to counter chemoresistance in OC.Show less >
Show more >Ovarian cancer (OC) is the leading cause of death in patients with gynecologic cancers. Due to late diagnosis and resistance to chemotherapy, the 5-year survival rate in patients with OC is below 40%. We observed that UCA1, a lncRNA previously reported to play an oncogenic role in several malignancies, is overexpressed in the chemoresistant OC cell line OAW42-R compared to their chemotherapy-sensitive counterpart OAW42. Additionally, UCA1 overexpression was related to poor prognosis in two independent patient cohorts. Currently, the molecular mechanisms through which UCA1 acts in OC are poorly understood. We demonstrated that downregulation of the short isoform of UCA1 sensitized OC cells to cisplatin and that UCA1 acted as competing endogenous RNA to miR-27a-5p. Upon UCA1 downregulation, miR-27a-5p downregulated its direct target UBE2N leading to the upregulation of BIM, a proapoptotic protein of the Bcl2 family. The upregulation of BIM is the event responsible for the sensitization of OC cells to cisplatin. In order to model response to therapy in patients with OC, we used several patient-derived organoid cultures, a model faithfully mimicking patient’s response to therapy. Inhibition of UBE2N sensitized patient-derived organoids to platinum salts. In conclusion, response to treatment in patients with OC is regulated by the UCA1/miR-27a-5p/UBE2N axis, where UBE2N inhibition could potentially represent a novel therapeutic strategy to counter chemoresistance in OC.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Submission date :
2023-12-21T07:12:08Z
2024-02-06T20:42:28Z
2024-02-06T20:42:28Z
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