The lncRNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR‐27a‐5p and control of UBE2N levels

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 malignanci...

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Autores principales:	Anaïs Wambecke, Mohammad Ahmad, Pierre‐Marie Morice, Bernard Lambert, Louis‐Bastien Weiswald, Mégane Vernon, Nicolas Vigneron, Edwige Abeilard, Emilie Brotin, Martin Figeac, Pascal Gauduchon, Laurent Poulain, Christophe Denoyelle, Matthieu Meryet‐Figuiere
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	ceRNA chemoresistance miR‐27a‐5p ovarian cancer patient‐derived organoid lncRNA UCA1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8a1e4e42fbc5491cb25a6a66c4690349
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spelling	oai:doaj.org-article:8a1e4e42fbc5491cb25a6a66c46903492021-12-02T10:31:06ZThe lncRNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR‐27a‐5p and control of UBE2N levels1878-02611574-789110.1002/1878-0261.13045https://doaj.org/article/8a1e4e42fbc5491cb25a6a66c46903492021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13045https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Ovarian 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.Anaïs WambeckeMohammad AhmadPierre‐Marie MoriceBernard LambertLouis‐Bastien WeiswaldMégane VernonNicolas VigneronEdwige AbeilardEmilie BrotinMartin FigeacPascal GauduchonLaurent PoulainChristophe DenoyelleMatthieu Meryet‐FiguiereWileyarticleceRNAchemoresistancemiR‐27a‐5povarian cancerpatient‐derived organoidlncRNA UCA1Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3659-3678 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ceRNA chemoresistance miR‐27a‐5p ovarian cancer patient‐derived organoid lncRNA UCA1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	ceRNA chemoresistance miR‐27a‐5p ovarian cancer patient‐derived organoid lncRNA UCA1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Anaïs Wambecke Mohammad Ahmad Pierre‐Marie Morice Bernard Lambert Louis‐Bastien Weiswald Mégane Vernon Nicolas Vigneron Edwige Abeilard Emilie Brotin Martin Figeac Pascal Gauduchon Laurent Poulain Christophe Denoyelle Matthieu Meryet‐Figuiere The lncRNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR‐27a‐5p and control of UBE2N levels
description	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.
format	article
author	Anaïs Wambecke Mohammad Ahmad Pierre‐Marie Morice Bernard Lambert Louis‐Bastien Weiswald Mégane Vernon Nicolas Vigneron Edwige Abeilard Emilie Brotin Martin Figeac Pascal Gauduchon Laurent Poulain Christophe Denoyelle Matthieu Meryet‐Figuiere
author_facet	Anaïs Wambecke Mohammad Ahmad Pierre‐Marie Morice Bernard Lambert Louis‐Bastien Weiswald Mégane Vernon Nicolas Vigneron Edwige Abeilard Emilie Brotin Martin Figeac Pascal Gauduchon Laurent Poulain Christophe Denoyelle Matthieu Meryet‐Figuiere
author_sort	Anaïs Wambecke
title	The lncRNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR‐27a‐5p and control of UBE2N levels
title_short	The lncRNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR‐27a‐5p and control of UBE2N levels
title_full	The lncRNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR‐27a‐5p and control of UBE2N levels
title_fullStr	The lncRNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR‐27a‐5p and control of UBE2N levels
title_full_unstemmed	The lncRNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR‐27a‐5p and control of UBE2N levels
title_sort	lncrna ‘uca1’ modulates the response to chemotherapy of ovarian cancer through direct binding to mir‐27a‐5p and control of ube2n levels
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/8a1e4e42fbc5491cb25a6a66c4690349
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The lncRNA ‘UCA1’ modulates the response to chemotherapy of ovarian cancer through direct binding to miR‐27a‐5p and control of UBE2N levels

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