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...

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Detalles Bibliográficos
Autores: 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, Reventós Puigjaner, Jaume, Rigau, Marina, Gil Moreno, Antonio, Segura, Miguel F., Santamaria Margalef, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat: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
Descripción
Sumario: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.

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