title: Identification and characterization of lncRNA mediated transcriptional dysregulation dictates lncRNA roles in glioblastoma.
abstract: Long non-coding RNAs (lncRNAs) modulate gene expression, and lncRNA misregulation is associated with cancer. However, precise functional roles in biological and disease processes have been described for only a few lncRNAs. Identification of genome-wide lncRNA-mediated transcriptional dysregulations may improve cancer treatments. In the present study, we used a computational framework that combined lncRNA and gene expression profiles with transcription factor (TF)-target relationships to comprehensively identify dysregulatory lncRNA-TF-gene triplets. In glioblastoma (GBM), we found that most lncRNAs affect multiple targets and primarily affect TF activity in trans. Six different classes of lncRNA-mediated transcriptional dysregulations were identified, with most lncRNAs either enhancing or attenuating target gene expression. Functional analysis of lncRNAs via their dysregulated targets implicated lncRNA modulators in some hallmarks of cancer, providing a new way to predict lncRNA function. Finally, we identified several lncRNA-TF-gene triplets (including HOTAIR-MXI1-CD58/PRKCE and HOTAIR-ATF5-NCAM1) that are associated with glioblastoma prognosis. The integration of lncRNA modulators into transcriptional regulatory networks will further enhance our understanding of lncRNA functions in cancer.
authors.affiliation: College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
authors.forename: Zishan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Lu
authors.affiliation: College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D062085:RNA, Long Noncoding / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D059467:Transcriptome
chemical_list: D062085:RNA, Long Noncoding; D014157:Transcription Factors
keywords: lncRNA modulator; lncRNA roles; lncRNA-TF-gene triplets; long non-coding RNA; transcriptional dysregulation