TY - JOUR
T1 - miR-135b suppresses tumorigenesis in glioblastoma stem-like cells impairing proliferation, migration and self-renewal
AU - Lulli, Valentina
AU - Buccarelli, Mariachiara
AU - Martini, Maurizio
AU - Signore, Michele
AU - Biffoni, Mauro
AU - Giannetti, Stefano
AU - Morgante, Liliana
AU - Marziali, Giovanna
AU - Ilari, Ramona
AU - Pagliuca, Alfredo
AU - Larocca, Luigi Maria
AU - De Maria Marchiano, Ruggero
AU - Pallini, Roberto
AU - Ricci-Vitiani, Lucia
PY - 2015
Y1 - 2015
N2 - Glioblastoma multiforme (GBM) is the most common and fatal malignant adult primary brain tumor. Currently, the overall prognosis for GBM patients remains poor despite advances in neurosurgery and adjuvant treatments. MicroRNAs (miRNAs) contribute to the pathogenesis of various types of tumor, including GBM. In this study we analyzed the expression of a panel of miRNAs, which are known to be differentially expressed by the brain and GBM tumor, in a collection of patient-derived GBM stem- like cells (GSCs). Notably, the average expression level of miR-135b, was the most downregulated compared to its normal counterpart, suggesting a potential role as anti-oncogene.
Restoration of miR-135b in GSCs signi cantly decreased proliferation, migration and clonogenic abilities. More importantly, miR-135b restoration was able to signi cantly reduce brain in ltration in mouse models of GBM obtained by intracerebral injection of GSC lines. We identi ed ADAM12 and con rmed SMAD5 and GSK3β as miR-135b targets and potential mediators of its effects. The whole transcriptome analysis ascertained that the expression of miR-135b downmodulated additional genes driving key pathways in GBM survival and in ltration capabilities.
Our results identify a critical role of miR-135b in the regulation of GBM development, suggesting that miR-135b might act as a tumor-suppressor factor and thus providing a potential candidate for the treatment of GBM patients.
AB - Glioblastoma multiforme (GBM) is the most common and fatal malignant adult primary brain tumor. Currently, the overall prognosis for GBM patients remains poor despite advances in neurosurgery and adjuvant treatments. MicroRNAs (miRNAs) contribute to the pathogenesis of various types of tumor, including GBM. In this study we analyzed the expression of a panel of miRNAs, which are known to be differentially expressed by the brain and GBM tumor, in a collection of patient-derived GBM stem- like cells (GSCs). Notably, the average expression level of miR-135b, was the most downregulated compared to its normal counterpart, suggesting a potential role as anti-oncogene.
Restoration of miR-135b in GSCs signi cantly decreased proliferation, migration and clonogenic abilities. More importantly, miR-135b restoration was able to signi cantly reduce brain in ltration in mouse models of GBM obtained by intracerebral injection of GSC lines. We identi ed ADAM12 and con rmed SMAD5 and GSK3β as miR-135b targets and potential mediators of its effects. The whole transcriptome analysis ascertained that the expression of miR-135b downmodulated additional genes driving key pathways in GBM survival and in ltration capabilities.
Our results identify a critical role of miR-135b in the regulation of GBM development, suggesting that miR-135b might act as a tumor-suppressor factor and thus providing a potential candidate for the treatment of GBM patients.
KW - ADAM12
KW - GSK3β
KW - Glioblastoma
KW - Glioblastoma stem cells
KW - SMAD5
KW - miRNAs
KW - ADAM12
KW - GSK3β
KW - Glioblastoma
KW - Glioblastoma stem cells
KW - SMAD5
KW - miRNAs
UR - http://hdl.handle.net/10807/111286
U2 - 10.18632/oncotarget.5925
DO - 10.18632/oncotarget.5925
M3 - Article
SN - 1949-2553
VL - 6
SP - 37241
EP - 37256
JO - Oncotarget
JF - Oncotarget
ER -