TY - JOUR
T1 - MicroRNAs in glioblastoma
T2 - Role in pathogenesis and opportunities for targeted therapies
AU - Costa, Pedro M.
AU - Cardoso, Ana L.
AU - Mano, Miguel
AU - de Lima, Maria C.Pedroso
N1 - Publisher Copyright:
© 2015 Bentham Science Publishers.
PY - 2015
Y1 - 2015
N2 - Glioblastoma (GBM) is among the most lethal human cancers, being generally characterized by rapid diffuse and infiltrative growth and high level of cellular heterogeneity associated with therapeutic resistance. Despite remarkable advances in cancer theranostics, which resulted in significant improvement of clinical outcomes, patient survival remains under one year. In recent years, considerable progress has been made in understanding the role of small non-coding RNAs, designated microRNAs, in the pathogenesis of GBM. Indeed, microRNAs were found to play a critical role in multiple steps of the tumorigenic process, including cellular proliferation, apoptosis evasion, invasion, angiogenesis, and stemness. Moreover, the modulation of microRNA expression, using either antisense oligonucleotides or precursor/mimic sequences, revealed a tremendous potential for application in GBM-targeted therapeutic approaches, either per se or in combination with chemo- and/or radiotherapy. In this manuscript, we review the regulatory role of microRNAs in key cellular processes underlying GBM tumorigenesis, including migration and invasion, apoptosis evasion, angiogenesis and GBM stem-like cell proliferation/differentiation, and discuss the current knowledge on their potential as diagnostic, prognostic and predictive biomarkers in this disease. We also address the latest advances in microRNA-based therapeutic approaches for GBM, by summarizing the major achievements in in vitro and pre-clinical studies. The trends identified by these studies are highlighted in order to provide new prospects for future developments towards the successful treatment of GBM.
AB - Glioblastoma (GBM) is among the most lethal human cancers, being generally characterized by rapid diffuse and infiltrative growth and high level of cellular heterogeneity associated with therapeutic resistance. Despite remarkable advances in cancer theranostics, which resulted in significant improvement of clinical outcomes, patient survival remains under one year. In recent years, considerable progress has been made in understanding the role of small non-coding RNAs, designated microRNAs, in the pathogenesis of GBM. Indeed, microRNAs were found to play a critical role in multiple steps of the tumorigenic process, including cellular proliferation, apoptosis evasion, invasion, angiogenesis, and stemness. Moreover, the modulation of microRNA expression, using either antisense oligonucleotides or precursor/mimic sequences, revealed a tremendous potential for application in GBM-targeted therapeutic approaches, either per se or in combination with chemo- and/or radiotherapy. In this manuscript, we review the regulatory role of microRNAs in key cellular processes underlying GBM tumorigenesis, including migration and invasion, apoptosis evasion, angiogenesis and GBM stem-like cell proliferation/differentiation, and discuss the current knowledge on their potential as diagnostic, prognostic and predictive biomarkers in this disease. We also address the latest advances in microRNA-based therapeutic approaches for GBM, by summarizing the major achievements in in vitro and pre-clinical studies. The trends identified by these studies are highlighted in order to provide new prospects for future developments towards the successful treatment of GBM.
KW - Glioblastoma
KW - Glioblastoma stem-like cells
KW - MicroRNA modulation
KW - MicroRNAs
KW - Oncogene
KW - Tumor suppressor
UR - http://www.scopus.com/inward/record.url?scp=84930907378&partnerID=8YFLogxK
U2 - 10.2174/1871527314666150116123610
DO - 10.2174/1871527314666150116123610
M3 - Article
C2 - 25613511
AN - SCOPUS:84930907378
SN - 1871-5273
VL - 14
SP - 222
EP - 238
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
IS - 2
ER -
