Oncotarget

Research Papers:

Identification and characterization of lncRNA mediated transcriptional dysregulation dictates lncRNA roles in glioblastoma

Yongsheng Li, Zishan Wang, Yuan Wang, Zheng Zhao, Jinwen Zhang, Jianping Lu, Juan Xu and Xia Li _

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Oncotarget. 2016; 7:45027-45041. https://doi.org/10.18632/oncotarget.7801

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Abstract

Yongsheng Li1,*, Zishan Wang1,*, Yuan Wang1,*, Zheng Zhao1, Jinwen Zhang1, Jianping Lu1, Juan Xu1, Xia Li1

1College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China

*These authors contributed equally to this work

Correspondence to:

Xia Li, email: lixia@hrbmu.edu.cn

Juan Xu, email: xujuanbiocc@ems.hrbmu.edu.cn

Keywords: long non-coding RNA, transcriptional dysregulation, lncRNA roles, lncRNA modulator, lncRNA-TF-gene triplets

Received: September 14, 2015     Accepted: January 27, 2016     Published: March 01, 2016

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.


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