Affordable Access

deepdyve-link
Publisher Website

Human glioma growth is controlled by microRNA-10b.

Authors
  • G, Gabriely
  • M, Yi
  • Rs, Narayan
  • Jm, Niers
  • T, Wurdinger
  • J, Imitola
  • Kl, Ligon
  • Santosh Kesari
  • C, Esau
  • Rm, Stephens
  • Ba, Tannous
  • Am, Krichevsky
Type
Published Article
Journal
Cancer Research
Publisher
American Association for Cancer Research
Volume
71
Issue
10
Pages
3563–3572
Identifiers
DOI: 10.1158/0008-5472.CAN-10-3568
Source
Kesari Lab
License
Unknown

Abstract

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

Report this publication

Statistics

Seen <100 times