Journal
NUCLEIC ACIDS RESEARCH
Volume 41, Issue 22, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkt1054
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Funding
- National Natural Science Foundation of China [81121003, 91129710, 61170154, 61203264]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20102307110022]
- China Postdoctoral Science Foundation [2012M520764]
- Heilongjiang Postdoctoral Fund [LBH-Z12214]
- Innovation Research Fund for Graduate Students of Heilongjiang province [YJSCX2012-196HLJ]
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Glioma is the most common and fatal primary brain tumour with poor prognosis; however, the functional roles of miRNAs in glioma malignant progression are insufficiently understood. Here, we used an integrated approach to identify miRNA functional targets during glioma malignant progression by combining the paired expression profiles of miRNAs and mRNAs across 160 Chinese glioma patients, and further constructed the functional miRNA-mRNA regulatory network. As a result, most tumour-suppressive miRNAs in glioma progression were newly discovered, whose functions were widely involved in gliomagenesis. Moreover, three miRNA signatures, with different combinations of hub miRNAs (regulations >= 30) were constructed, which could independently predict the survival of patients with all gliomas, high-grade glioma and glioblastoma. Our network-based method increased the ability to identify the prognostic biomarkers, when compared with the traditional method and random conditions. Hsa-miR-524-5p and hsa-miR-628-5p, shared by these three signatures, acted as protective factors and their expression decreased gradually during glioma progression. Functional analysis of these miRNA signatures highlighted their critical roles in cell cycle and cell proliferation in glioblastoma malignant progression, especially hsa-miR-524-5p and hsa-miR-628-5p exhibited dominant regulatory activities. Therefore, network-based biomarkers are expected to be more effective and provide deep insights into the molecular mechanism of glioma malignant progression.
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