Journal Article

The Putative Tumor Suppressor miR-524–5p Directly Targets Jagged-1 and Hes-1 in Glioma

Lingchao Chen, Wei Zhang, Wei Yan, Lei Han, Kailiang Zhang, Zhendong Shi, Junxia Zhang, Yongzhi Wang, Yongli Li, Shizhu Yu, Peiyu Pu, Chuanlu Jiang, Tao Jiang and Chunsheng Kang

in Carcinogenesis

Volume 33, issue 11, pages 2276-2282
Published in print November 2012 | ISSN: 0143-3334
Published online July 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs261
The Putative Tumor Suppressor miR-524–5p Directly Targets Jagged-1 and Hes-1 in Glioma

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Notch pathway plays critical role in stem cell maintenance and angiogenesis, as well as cell fate decisions of cancer. However, concrete mechanisms of notch pathway regulation in glioma were not well known, especially mediated by microRNAs. In this study, we identified a brain-specific miRNA, miR-524–5p, which was associated with the pathological grade and overall survival of gliomas. Restorated expression of miR-524–5p in glioma suppressed cell proliferation and invasion both in vitro and in vivo. Using bioinformatics and biological approaches, we found that Jagged-1 and Hes-1, two key components of notch pathway, were direct targets of miR-524–5p. Knocking down of Jagged-1 or Hes-1 partially phenocopied miR-524–5p re-expression, whereas forced expression of Jagged-1 or Hes-1 reversed the effects of miR-524–5p on proliferation and invasion of glioma. Moreover, miR-524–5p levels in glioma samples were inversely correlated with Jagged-1 and Hes-1 and their overexpressions were associated with poor survival. Thus, we have identified that miR-524–5p behaves as a tumor suppressor by negatively targeting Jagged-1 and Hes-1 and provides an additional option to inhibit this oncogene in gliomas.

Journal Article.  4581 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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