Oncotarget

Research Papers:

microRNA-149 targets caspase-2 in glioma progression

Xiaokun Shen, Jie Li, Wenfeng Liao, Jiwen Wang, Huanjun Chen, Yanli Yao, Houbao Liu _ and Kan Ding

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Oncotarget. 2016; 7:26388-26399. https://doi.org/10.18632/oncotarget.8506

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Abstract

Xiaokun Shen1,*, Jie Li1,*, Wenfeng Liao1, Jiwen Wang2, Huanjun Chen1, Yanli Yao1, Houbao Liu2, Kan Ding1

1Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

2Department of General Surgery, Zhongshan Hospital, General Surgery Institute, Fudan University, Shanghai 200032, China

*These authors contributed equally to this work

Correspondence to:

Houbao Liu, email: [email protected]

Kan Ding, email: [email protected]

Keywords: glioma, microRNA-149, caspase-2, p53

Received: September 13, 2015     Accepted: February 05, 2016     Published: March 30, 2016

ABSTRACT

Malignant gliomas are the most common form of intrinsic primary brain tumors worldwide. Alterations in microRNAs play a role in highly invasive malignant glioma, but detail mechanism still unknown. In this study, the role and mechanism of microRNA-149 (miR-149) in glioma are investigated. We show that miR-149 is expressed at substantially higher levels in glioma than in normal tissues. Stable overexpression of miR-149 augments potent prosurvival activity, as evidenced by promotion of cell viability, inhibition of apoptosis, and induced xenografted tumor growth in vivo. We further show that Caspase-2 is identified as a functional target of miR-149 and expression of caspase-2 is inversely associated with miR-149 in vitro. In addition, miR-149 promotes tumor survival in the U87-MG and A172 cell lines and it targets caspase-2 via inactivation of the p53 and p21 pathways. There results support a special role for miR-149 by targeting Caspase-2 to impact on p53 signaling pathway. We speculate that miR-149 has distinct biological functions in p53 wild type cells and p53 mutation cells, and the mechanisms involved remain to be explored in future. Our study suggests that targeting miR-149 may be a novel therapy strategy for treating p53 wild type glioma tumors in humans.


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