TY - JOUR
T1 - MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cells
AU - Gal, Hilah
AU - Pandi, Gopal
AU - Kanner, Andrew A.
AU - Ram, Zvi
AU - Lithwick-Yanai, Gila
AU - Amariglio, Ninette
AU - Rechavi, Gideon
AU - Givol, David
PY - 2008/11/7
Y1 - 2008/11/7
N2 - We examined the microRNA profiles of Glioblastoma stem (CD133+) and non-stem (CD133-) cell populations and found up-regulation of several miRs in the CD133- cells, including miR-451, miR-486, and miR-425, some of which may be involved in regulation of brain differentiation. Transfection of GBM cells with the above miRs inhibited neurosphere formation and transfection with the mature miR-451 dispersed neurospheres, and inhibited GBM cell growth. Furthermore, transfection of miR-451 combined with Imatinib mesylate treatment had a cooperative effect in dispersal of GBM neurospheres. In addition, we identified a target site for SMAD in the promoter region of miR-451 and showed that SMAD3 and 4 activate such a promoter-luciferase construct. Transfection of SMAD in GBM cells inhibited their growth, suggesting that SMAD may drive GBM stem cells to differentiate to CD133- cells through up-regulation of miR-451 and reduces their tumorigenicity. Identification of additional miRs and target genes that regulate GBM stem cells may provide new potential drugs for therapy.
AB - We examined the microRNA profiles of Glioblastoma stem (CD133+) and non-stem (CD133-) cell populations and found up-regulation of several miRs in the CD133- cells, including miR-451, miR-486, and miR-425, some of which may be involved in regulation of brain differentiation. Transfection of GBM cells with the above miRs inhibited neurosphere formation and transfection with the mature miR-451 dispersed neurospheres, and inhibited GBM cell growth. Furthermore, transfection of miR-451 combined with Imatinib mesylate treatment had a cooperative effect in dispersal of GBM neurospheres. In addition, we identified a target site for SMAD in the promoter region of miR-451 and showed that SMAD3 and 4 activate such a promoter-luciferase construct. Transfection of SMAD in GBM cells inhibited their growth, suggesting that SMAD may drive GBM stem cells to differentiate to CD133- cells through up-regulation of miR-451 and reduces their tumorigenicity. Identification of additional miRs and target genes that regulate GBM stem cells may provide new potential drugs for therapy.
KW - Combination therapy
KW - MicroRNA
KW - Neurospheres
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=52049096593&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.08.107
DO - 10.1016/j.bbrc.2008.08.107
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 18765229
AN - SCOPUS:52049096593
SN - 0006-291X
VL - 376
SP - 86
EP - 90
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -