miR128-1 inhibits the growth of glioblastoma multiforme and glioma stem-like cells via targeting BMI1 and E2F3
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Date
2016
Authors
Shan, Z.N.
Tian, R.
Zhang, M.
Gui, Z.H.
Wu, J.
Ding, M.
Zhou, X.F.
He, J.
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Journal article
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Oncotarget, 2016; 7(48):78813-78826
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Abstract
MicroRNA128-1 (miR128-1), as a brain-specific miRNA, is down regulated in glioblastoma multiforme (GBM) and closely associated with the progression of GBM. However, the underlying molecular mechanism of the down regulation and its role in the regulation of tumorigenesis and anticancer drug resistance in GBM remains largely unknown. In the current study,we found that miR128-1 was down regulated in GBM and glioma stem-like cells (GSCs). Intriguingly, treatment with the DNA methylation inhibitors 5-Aza-CdR (Aza) and 4-phenylbutyric acid (PBA) resulted in miR128-1 up regulation in both GBM cells and GSCs. Either forced expression of miR128-1 or Aza/PBA treatment inhibited tumor cell proliferation, migration and invasion in vitro. Moreover, overexpression of miR128-1 inhibited the growth of transplant tumor in vivo. BMI1 and E2F3 were found to be direct targets of miR128-1 and down regulated by miR128-1 in vitro and in vivo. Our results revealed a mechanism of methylation that controls miR128-1 expression in GBM cells and GSCs and indicate miR128-1 could function as a tumor suppressor in GBM by negatively regulating tumor cell proliferation, invasion and self-renewal through direct targeting BMI1 and E2F3. Our findings suggest that DNA methylation inhibitors are potential agents for GBM treatment by up regulating miR-128-1.
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Copyright 2016 the author(s). Oncotarget applies the Creative Commons Attribution License (CC BY) to all works we publish (read the human-readable summary or the full license legal code). Under the CC BY, authors retain ownership of the copyright for their article, but authors allow anyone to download, reuse, reprint, modify, distribute, and/or copy articles in Oncotarget, so long as the original authors and source are cited. (https://creativecommons.org/licenses/by/3.0/)