作者: Galina Gabriely , Ming Yi , Ravi S. Narayan , Johanna M. Niers , Thomas Wurdinger
DOI: 10.1158/0008-5472.CAN-10-3568
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摘要: MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions these gliomagenesis are mainly unknown. We show that inhibition miR-10b, miRNA not expressed human and strongly upregulated both low-grade high-grade gliomas, reduces glioma cell growth by cell-cycle arrest apoptosis. These cellular responses mediated augmented direct targets including BCL2L11/Bim, TFAP2C/AP-2γ, CDKN1A/p21, CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis The Cancer Genome Atlas data set reveals strong positive correlation between numerous genes sustaining miR-10b levels glioblastomas, while proapoptotic anticorrelate with miR-10b. Furthermore, survival glioblastoma patients expressing high miR-10 family members is significantly reduced comparison to low levels, indicating may contribute vivo. Finally, mouse model results significant reduction Altogether, our experiments validate an important role gliomagenesis, reveal novel mechanism miR-10b-mediated regulation, suggest possibility its future use as therapeutic target gliomas.