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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01055

Identification of dysregulated competitive endogenous RNA networks driven by copy number variations in malignant gliomas

 Jinyuan Xu1, Xiaobo Hou1, Lin Pang1, Shangqin Sun1, Shenyuan He1, Yiran Yang1, Kun Liu1,  Linfu Xu1, Wenkang Yin1,  Chaohan Xu1* and  Yun Xiao1*
  • 1Harbin Medical University, China

Gliomas represent 80% of malignant brain tumors. Because of the high heterogeneity, the oncogenic mechanisms in gliomas are still unclear. In this study, we developed a new approach to identify dysregulated competitive endogenous RNA (ceRNA) interactions driven by copy number variation (CNV) in both lower grade glioma (LGG) and glioblastoma multiforme (GBM). By analyzing genome and transcriptome data from The Cancer Genome Atlas (TCGA), we first found out the protein coding genes and long non-coding RNAs (lncRNAs) significantly affected by CNVs and further determined CNV-driven dysregulated ceRNA interactions by a customized pipeline. We obtained 13,776 CNV-driven dysregulated ceRNA pairs (including 3,954 mRNAs and 306 lncRNAs) in LGG and 262 pairs (including 221 mRNAs and 11 lncRNAs) in GBM, respectively. Our results showed that most of the ceRNA interactions were weakened by CNVs in both LGG and GBM, and many CNV-driven genes shared the same ceRNAs in the dysregulated ceRNA networks. Functional analysis indicated that the CNV-driven ceRNA network involved in some important mechanisms of tumorigenesis, such as cell cycle, p53 signaling pathway and TGF-beta signaling pathway. Further investigation of the ceRNA pairs in the communities from the dysregulated ceRNA network revealed more detailed biological functions related to the oncogenesis of malignant gliomas. Moreover, by exploring the association of CNV-driven ceRNAs with prognosis and histological subtype, we found that the copy number status of MTAP, KLHL9 and ELAVL2 related to the overall survival in LGG and showed high correlation with histological subtype. In conclusion, this study provided new insight into the molecular mechanisms and clinical biomarkers in gliomas.

Keywords: gliomas, CNV, ceRNA, lncRNA, prognosis

Received: 23 May 2019; Accepted: 01 Oct 2019.

Copyright: © 2019 Xu, Hou, Pang, Sun, He, Yang, Liu, Xu, Yin, Xu and Xiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Chaohan Xu, Harbin Medical University, Harbin, 130012, Heilongjiang, China, chaohanxu@hrbmu.edu.cn
Mx. Yun Xiao, Harbin Medical University, Harbin, 130012, Heilongjiang, China, xiaoyun@ems.hrbmu.edu.cn