TY - JOUR
T1 - Potential role of mirnas in the acquisition of chemoresistance in neuroblastoma
AU - Marengo, Barbara
AU - Pulliero, Alessandra
AU - Corrias, Maria Valeria
AU - Leardi, Riccardo
AU - Farinini, Emanuele
AU - Fronza, Gilberto
AU - Menichini, Paola
AU - Monti, Paola
AU - Monteleone, Lorenzo
AU - Valenti, Giulia Elda
AU - Speciale, Andrea
AU - Perri, Patrizia
AU - Madia, Francesca
AU - Izzotti, Alberto
AU - Domenicotti, Cinzia
N1 - Funding Information:
Funding: This research was supported by the University of Genoa and by the Italian Association for Cancer research (AIRC) IG-2017 Id.20699.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Neuroblastoma (NB) accounts for about 8–10% of pediatric cancers, and the main causes of death are the presence of metastases and the acquisition of chemoresistance. Metastatic NB is characterized by MYCN amplification that correlates with changes in the expression of miRNAs, which are small non-coding RNA sequences, playing a crucial role in NB development and chemoresistance. In the present study, miRNA expression was analyzed in two human MYCN-amplified NB cell lines, one sensitive (HTLA-230) and one resistant to Etoposide (ER-HTLA), by microarray and RT-qPCR techniques. These analyses showed that miRNA-15a,-16-1,-19b,-218, and-338 were down-regulated in ER-HTLA cells. In order to validate the presence of this down-regulation in vivo, the expression of these miRNAs was analyzed in primary tumors, metastases, and bone marrow of therapy responder and non-responder pediatric patients. Principal component analysis data showed that the expression of miRNA-19b,-218, and-338 influenced metastases, and that the expression levels of all miRNAs analyzed were higher in therapy responders in respect to non-responders. Collectively, these findings suggest that these miRNAs might be involved in the regulation of the drug response, and could be employed for therapeutic purposes.
AB - Neuroblastoma (NB) accounts for about 8–10% of pediatric cancers, and the main causes of death are the presence of metastases and the acquisition of chemoresistance. Metastatic NB is characterized by MYCN amplification that correlates with changes in the expression of miRNAs, which are small non-coding RNA sequences, playing a crucial role in NB development and chemoresistance. In the present study, miRNA expression was analyzed in two human MYCN-amplified NB cell lines, one sensitive (HTLA-230) and one resistant to Etoposide (ER-HTLA), by microarray and RT-qPCR techniques. These analyses showed that miRNA-15a,-16-1,-19b,-218, and-338 were down-regulated in ER-HTLA cells. In order to validate the presence of this down-regulation in vivo, the expression of these miRNAs was analyzed in primary tumors, metastases, and bone marrow of therapy responder and non-responder pediatric patients. Principal component analysis data showed that the expression of miRNA-19b,-218, and-338 influenced metastases, and that the expression levels of all miRNAs analyzed were higher in therapy responders in respect to non-responders. Collectively, these findings suggest that these miRNAs might be involved in the regulation of the drug response, and could be employed for therapeutic purposes.
KW - Chemoresistance
KW - Metastases
KW - MiRNA
KW - MYCN amplification
KW - Neuroblastoma
UR - http://www.scopus.com/inward/record.url?scp=85100710486&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100710486&partnerID=8YFLogxK
U2 - 10.3390/jpm11020107
DO - 10.3390/jpm11020107
M3 - Article
AN - SCOPUS:85100710486
VL - 11
SP - 1
EP - 17
JO - Journal of Personalized Medicine
JF - Journal of Personalized Medicine
SN - 2075-4426
IS - 2
M1 - 107
ER -