1. Identification of a Core miRNA-Pathway Regulatory Network in Glioma by Therapeutically Targeting miR-181d, miR-21, miR-23b, β-Catenin, CBP, and STAT3
- Author
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Xiang Li, Lei Han, Shangwei Ning, Chunsheng Kang, Jingrun Ye, Xia Li, and Ronghong Li
- Subjects
STAT3 Transcription Factor ,Microarrays ,Sialoglycoproteins ,lcsh:Medicine ,Biological Data Management ,Biology ,Research and Analysis Methods ,Bioinformatics ,Deep sequencing ,Cell Line, Tumor ,Glioma ,microRNA ,Gene expression ,medicine ,Humans ,Gene Regulatory Networks ,Molecular Targeted Therapy ,lcsh:Science ,STAT3 ,beta Catenin ,Computational Neuroscience ,Regulation of gene expression ,Multidisciplinary ,Brain Neoplasms ,Sequence Analysis, RNA ,Systems Biology ,lcsh:R ,Computational Biology ,High-Throughput Nucleotide Sequencing ,Biology and Life Sciences ,medicine.disease ,Peptide Fragments ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Crosstalk (biology) ,Bioassays and Physiological Analysis ,Catenin ,Cancer research ,biology.protein ,lcsh:Q ,Research Article - Abstract
The application of microRNAs (miRNAs) in the therapeutics of glioma and other human diseases is an area of intense interest. However, it’s still a great challenge to interpret the functional consequences of using miRNAs in glioma therapy. Here, we examined paired deep sequencing expression profiles of miRNAs and mRNAs from human glioma cell lines after manipulating the levels of miRNAs miR-181d, -21, and -23b, as well as transcriptional regulators β-catenin, CBP, and STAT3. An integrated approach was used to identify functional miRNA-pathway regulatory networks (MPRNs) responding to each manipulation. MiRNAs were identified to regulate glioma related biological pathways collaboratively after manipulating the level of either post-transcriptional or transcriptional regulators, and functional synergy and crosstalk was observed between different MPRNs. MPRNs responsive to multiple interventions were found to occupy central positions in the comprehensive MPRN (cMPRN) generated by integrating all the six MPRNs. Finally, we identified a core module comprising 14 miRNAs and five pathways that could predict the survival of glioma patients and represent potential targets for glioma therapy. Our results provided novel insight into miRNA regulatory mechanisms implicated in therapeutic interventions and could offer more inspiration to miRNA-based glioma therapy.
- Published
- 2014