title: Comprehensive analysis of the functional microRNA-mRNA regulatory network identifies miRNA signatures associated with glioma malignant progression.
abstract: 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.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150080, China, Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing 100050, China, College of Fundamental Medical Sciences, Harbin Medical University, Harbin 150080, China and 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 300052, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.forename: Shengli
authors.initials: S
authors.lastname: Li
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.forename: Tingting
authors.initials: T
authors.lastname: Shao
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Huan
authors.initials: H
authors.lastname: Ren
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002648:Child; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D023281:Genomics; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger