TY - JOUR
T1 - Comprehensive analysis of the functional microRNA-mRNA regulatory network identifies miRNA signatures associated with glioma malignant progression
AU - Li, Yongsheng
AU - Xu, Juan
AU - Chen, Hong
AU - Bai, Jing
AU - Li, Shengli
AU - Zhao, Zheng
AU - Shao, Tingting
AU - Jiang, Tao
AU - Ren, Huan
AU - Kang, Chunsheng
AU - Li, Xia
N1 - Funding Information:
The Innovation Research Fund for Graduate Students of Heilongjiang province [YJSCX2012-196HLJ]. Funding for open access charge: Funds for Creative Research Groups of The National Natural Science Foundation of China [81121003]; National Natural Science Foundation of China [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]; The Innovation Research Fund for Graduate Students of Heilongjiang province [YJSCX2012-196HLJ].
PY - 2013/12
Y1 - 2013/12
N2 - 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 hsamiR-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.
AB - 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 hsamiR-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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U2 - 10.1093/nar/gkt1054
DO - 10.1093/nar/gkt1054
M3 - Article
C2 - 24194606
AN - SCOPUS:84890391023
SN - 0305-1048
VL - 41
SP - e203
JO - Nucleic acids research
JF - Nucleic acids research
IS - 22
ER -