title: Identification of a core miRNA-pathway regulatory network in glioma by therapeutically targeting miR-181d, miR-21, miR-23b, β-Catenin, CBP, and STAT3.
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.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Ronghong
authors.initials: R
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Shangwei
authors.initials: S
authors.lastname: Ning
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Jingrun
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D058990:Molecular Targeted Therapy; D010446:Peptide Fragments / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics; D017423:Sequence Analysis, RNA; D012795:Sialoglycoproteins / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: C524940:MIRN21 microRNA, human; C552430:MIRN23a microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D010446:Peptide Fragments; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012795:Sialoglycoproteins; D051176:beta Catenin; C571744:bone sialoprotein (35-62), human