Research Papers:

miR128-1 inhibits the growth of glioblastoma multiforme and glioma stem-like cells via targeting BMI1 and E2F3

Zheng-nan Shan, Rui Tian, Min Zhang, Zhao-hua Gui, Jing Wu, Min Ding, Xin-Fu Zhou and Jie He _

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Oncotarget. 2016; 7:78813-78826. https://doi.org/10.18632/oncotarget.12385

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Zheng-nan Shan1,2, Rui Tian1, Min Zhang1, Zhao-hua Gui1, Jing Wu1, Min Ding1, Xin-Fu Zhou2, Jie He1

1Department of Pathology, Anhui Provincial Hospital affiliated to Anhui Medical University and Anhui Provincial Cancer Hospital, Hefei 230031, China

2School of Pharmacy and Medical Sciences, Faculty of Health Sciences, University of South Australia, Adelaide SA 5000, Australia

Correspondence to:

Jie He, email: hejie2005g@sina.com

Keywords: miR128-1, BMI1, E2F3, DNA methylation, glioblastoma multiforme

Received: April 13, 2016    Accepted: September 25, 2016    Published: October 1, 2016


MicroRNA128-1 (miR128-1), as a brain-specific miRNA, is downregulated in glioblastoma multiforme (GBM) and closely associated with the progression of GBM. However, the underlying molecular mechanism of the downregulation 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 downregulated 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 upregulation 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 downregulated 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 upregulating miR-128-1.

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