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Cancer Lett. 2014 Dec 1;355(1):85-95. doi: 10.1016/j.canlet.2014.09.012. Epub 2014 Sep 10.

MiR-152 functions as a tumor suppressor in glioblastoma stem cells by targeting Krüppel-like factor 4.

Author information

1
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
2
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
3
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China. Electronic address: xueyixue888@163.com.

Abstract

Glioblastoma (GBM) is the most common central nervous system tumor and the molecular mechanism driving its development is still largely unknown, limiting the treatment of this disease. In the present study, we explored the potential role of miR-152 in glioblastoma stem cells (GSCs) as well as the possible molecular mechanisms. Our results proved that miR-152 was down-regulated in human GSCs. Restoring the expression of miR-152 dramatically reduced the cell proliferation, cell migration and invasion as well as inducing apoptosis. Mechanistic investigations defined Krüppel-like factor 4 (KLF4) as a direct and functional downstream target of miR-152, which was involved in the miR-152-mediated tumor-suppressive effects in GSCs. Meanwhile, this process was coincided with the down-regulated LGALS3 that could be bound and promoted by KLF4, leading to attenuate the activation of MEK1/2 and PI3K signal pathways. Moreover, the in vivo study showed that miR-152 over-expression and KLF4 knockdown produced the smallest tumor volume and the longest survival in nude mice. Taken together, these results elucidated the function of miR-152 in GSCs progression and suggested a promising application of it in glioma treatment.

KEYWORDS:

Glioblastoma; KLF4; MiR-152; MicroRNAs; Stem cells

PMID:
25218589
DOI:
10.1016/j.canlet.2014.09.012
[Indexed for MEDLINE]

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