Oncotarget

Research Papers:

MicroRNA-564 is downregulated in glioblastoma and inhibited proliferation and invasion of glioblastoma cells by targeting TGF-β1

Chunming Jiang, Fang Shen, Jianmin Du, Zhaoyang Hu, Xiaoli Li, Jin Su, Xiaohua Wang and Xianmei Huang _

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Oncotarget. 2016; 7:56200-56208. https://doi.org/10.18632/oncotarget.8987

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Abstract

Chunming Jiang1,*, Fang Shen2,*, Jianmin Du1, Zhaoyang Hu3, Xiaoli Li1, Jin Su4, Xiaohua Wang5, Xianmei Huang1

1Department of Pediatrics, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou, Zhejiang 310003, P.R. China

2Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China

3Translational Medicine Office of Hangzhou Cancer Institute, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou, Zhejiang 310003, P.R. China

4Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China

5Department of Pediatrics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China

*Chunming Jiang and Fang Shen are co-first authors

Correspondence to:

Xianmei Huang, e-mail: hxianmei630715@163.com

Keywords: glioblastoma, microRNA-564, TGF-β, proliferation

Received: September 05, 2015    Accepted: January 23, 2016    Published: April 26, 2016

ABSTRACT

Increasing evidence has indicated that aberrant expression of miRNAs has been shown to be strongly implicated in the initiation and progression of glioblastoma. Here, we identified a novel tumor suppressive miRNA, miR-564, and investigated its role and therapeutic effect for glioblastoma. We showed that miR-564 was down-regulated in human glioblastoma tissues and cell lines. Introduction of miR-564 dramatically inhibited cell growth and invasion in glioblastoma cells. Subsequent experiments revealed that Transforming growth factor-β1 (TGF-β1) was a direct and functional target of miR-564 in glioblastoma cells. Furthermore, overexpression of miR-564 decreased p-SMAD and SMAD4 expression, which are the downstream signaling molecules of TGF-β. Meanwhile, ectopic of miR-564 reduced the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9. Furthermore, the upregulation of miR-564 suppressed TGF-β-mediated U87 proliferation and migration. The expression of EGFR and MMP9 was upregulated in glioblastoma tissues compared to their normal tissues. The EGFR and MMP9 expression levels were inverse correlated with the expression of miR-564. miR-564 suppressed the growth of U87-engrafted tumors. These findings reveal that miR-564/TGF-β1 signaling that may be required for glioblastoma development and may consequently serve as a new therapeutic target for the treatment of glioblastoma.


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