MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathways
Ovarian cancer is the most lethal gynecological malignancy due to the silent nature on its early onset and the rapid acquisition of drug resistance. Histologically heterogeneous, it includes several subtypes with different mutational landscapes, hampering the development of effective targeted therap...
| Autores: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/147966 |
| Acceso en línea: | https://hdl.handle.net/2445/147966 |
| Access Level: | acceso abierto |
| Palabra clave: | Apoptosi Epigenètica Micro RNAs Càncer d'ovari Apoptosis Epigenetics MicroRNAs Ovarian cancer |
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MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathwaysMajem, BlancaParrilla, AlfonsoJiménez, CarlosMarin, AndreaSuárez, LeticiaCastellví, JosepTamayo, GabrielMoreno, GemaPonce i Sebastià, JordiMatias-Guiu, Xavier, 1958-Alameda, FrancescRomero, IgnacioSánchez, José LuisPérez Benavente, AsunciónMoran, SebastianEsteller, Manel, 1968-Reventós Puigjaner, JaumeRigau, MarinaGil Moreno, AntonioSegura, Miguel F.Santamaria Margalef, AnnaApoptosiEpigenèticaMicro RNAsCàncer d'ovariApoptosisEpigeneticsMicroRNAsOvarian cancerOvarian cancer is the most lethal gynecological malignancy due to the silent nature on its early onset and the rapid acquisition of drug resistance. Histologically heterogeneous, it includes several subtypes with different mutational landscapes, hampering the development of effective targeted therapies. Non-coding RNAs are emerging as potential new therapeutic targets in cancer. To search for a microRNA signature related to ovarian carcinomas and study its potential as effective targeted therapy, we examined the expression of 768 miRNA in a large collection of tumor samples and found miR-654-5p to be infraexpressed in ovarian serous carcinomas, the most common and aggressive type. Restoration of miR654-5p levels reduced tumor cell viability in vitro and in vivo and impaired sphere formation capacity and viability of ovarian cancer patient-derived ascitic cells ex vivo. CDCP1 and PLAGL2 oncogenes were found to be the most relevant direct miR-654-5p targets and both genes convey in a molecular signature associated with key cancer pathways relevant to ovarian tumorigenesis, such as MYC, WNT and AKT pathways. Together, we unveiled the tumor suppressor function of miR-654-5p, suggesting that its restoration or co-targeting of CDCP1 and PLAGL2 may be an effective therapeutic approach for ovarian cancer.National Academy of Sciences2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/147966Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41388-019-0860-0Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2019, vol. 38, p. 6035-6050https://doi.org/10.1038/s41388-019-0860-0(c) Majem, Blanca et al., 2019info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1479662026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathways |
| title |
MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathways |
| spellingShingle |
MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathways Majem, Blanca Apoptosi Epigenètica Micro RNAs Càncer d'ovari Apoptosis Epigenetics MicroRNAs Ovarian cancer |
| title_short |
MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathways |
| title_full |
MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathways |
| title_fullStr |
MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathways |
| title_full_unstemmed |
MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathways |
| title_sort |
MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC; WNT and AKT pathways |
| dc.creator.none.fl_str_mv |
Majem, Blanca Parrilla, Alfonso Jiménez, Carlos Marin, Andrea Suárez, Leticia Castellví, Josep Tamayo, Gabriel Moreno, Gema Ponce i Sebastià, Jordi Matias-Guiu, Xavier, 1958- Alameda, Francesc Romero, Ignacio Sánchez, José Luis Pérez Benavente, Asunción Moran, Sebastian Esteller, Manel, 1968- Reventós Puigjaner, Jaume Rigau, Marina Gil Moreno, Antonio Segura, Miguel F. Santamaria Margalef, Anna |
| author |
Majem, Blanca |
| author_facet |
Majem, Blanca Parrilla, Alfonso Jiménez, Carlos Marin, Andrea Suárez, Leticia Castellví, Josep Tamayo, Gabriel Moreno, Gema Ponce i Sebastià, Jordi Matias-Guiu, Xavier, 1958- Alameda, Francesc Romero, Ignacio Sánchez, José Luis Pérez Benavente, Asunción Moran, Sebastian Esteller, Manel, 1968- Reventós Puigjaner, Jaume Rigau, Marina Gil Moreno, Antonio Segura, Miguel F. Santamaria Margalef, Anna |
| author_role |
author |
| author2 |
Parrilla, Alfonso Jiménez, Carlos Marin, Andrea Suárez, Leticia Castellví, Josep Tamayo, Gabriel Moreno, Gema Ponce i Sebastià, Jordi Matias-Guiu, Xavier, 1958- Alameda, Francesc Romero, Ignacio Sánchez, José Luis Pérez Benavente, Asunción Moran, Sebastian Esteller, Manel, 1968- Reventós Puigjaner, Jaume Rigau, Marina Gil Moreno, Antonio Segura, Miguel F. Santamaria Margalef, Anna |
| author2_role |
author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Apoptosi Epigenètica Micro RNAs Càncer d'ovari Apoptosis Epigenetics MicroRNAs Ovarian cancer |
| topic |
Apoptosi Epigenètica Micro RNAs Càncer d'ovari Apoptosis Epigenetics MicroRNAs Ovarian cancer |
| description |
Ovarian cancer is the most lethal gynecological malignancy due to the silent nature on its early onset and the rapid acquisition of drug resistance. Histologically heterogeneous, it includes several subtypes with different mutational landscapes, hampering the development of effective targeted therapies. Non-coding RNAs are emerging as potential new therapeutic targets in cancer. To search for a microRNA signature related to ovarian carcinomas and study its potential as effective targeted therapy, we examined the expression of 768 miRNA in a large collection of tumor samples and found miR-654-5p to be infraexpressed in ovarian serous carcinomas, the most common and aggressive type. Restoration of miR654-5p levels reduced tumor cell viability in vitro and in vivo and impaired sphere formation capacity and viability of ovarian cancer patient-derived ascitic cells ex vivo. CDCP1 and PLAGL2 oncogenes were found to be the most relevant direct miR-654-5p targets and both genes convey in a molecular signature associated with key cancer pathways relevant to ovarian tumorigenesis, such as MYC, WNT and AKT pathways. Together, we unveiled the tumor suppressor function of miR-654-5p, suggesting that its restoration or co-targeting of CDCP1 and PLAGL2 may be an effective therapeutic approach for ovarian cancer. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/147966 |
| url |
https://hdl.handle.net/2445/147966 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1038/s41388-019-0860-0 Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2019, vol. 38, p. 6035-6050 https://doi.org/10.1038/s41388-019-0860-0 |
| dc.rights.none.fl_str_mv |
(c) Majem, Blanca et al., 2019 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) Majem, Blanca et al., 2019 |
| eu_rights_str_mv |
openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
National Academy of Sciences |
| publisher.none.fl_str_mv |
National Academy of Sciences |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Ciències Clíniques) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
| instname_str |
Universidad de Barcelona |
| reponame_str |
Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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1869409170733662208 |
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15,300719 |