TY - JOUR
T1 - MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC, WNT and AKT pathways
AU - Majem, Blanca
AU - Parrilla, Alfonso
AU - Jiménez, Carlos
AU - Suárez-Cabrera, Leticia
AU - Barber, Marta
AU - Marín, Andrea
AU - Castellví, Josep
AU - Tamayo, Gabriel
AU - Moreno-Bueno, Gema
AU - Ponce, Jordi
AU - Matias-Guiu, Xavier
AU - Alameda, Francesc
AU - Romero, Ignacio
AU - Sánchez, José Luis
AU - Pérez-Benavente, Asunción
AU - Moran, Sebastián
AU - Esteller, Manel
AU - Reventós, Jaume
AU - Rigau, Marina
AU - Gil-Moreno, Antonio
AU - Segura, Miguel F.
AU - Santamaría, Anna
PY - 2019/8/8
Y1 - 2019/8/8
N2 - © 2019, The Author(s), under exclusive licence to Springer Nature Limited. 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 miR-654-5p 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.
AB - © 2019, The Author(s), under exclusive licence to Springer Nature Limited. 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 miR-654-5p 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.
UR - http://www.mendeley.com/research/microrna6545p-suppresses-ovarian-cancer-development-impacting-myc-wnt-akt-pathways
U2 - 10.1038/s41388-019-0860-0
DO - 10.1038/s41388-019-0860-0
M3 - Article
C2 - 31278368
SN - 0950-9232
VL - 38
SP - 6035
EP - 6050
JO - Oncogene
JF - Oncogene
ER -