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Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer

Author

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  • Zhou Du

    (Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital
    School of Life Sciences and Technology, Tongji University)

  • Tong Sun

    (Dana-Farber Cancer Institute
    Harvard Medical School, Boston
    University of Massachusetts Medical School)

  • Ezgi Hacisuleyman

    (Harvard University
    Harvard University
    Broad Institute of Massachusetts Institute of Technology and Harvard)

  • Teng Fei

    (Dana-Farber Cancer Institute
    Harvard Medical School, Boston
    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute)

  • Xiaodong Wang

    (Dana-Farber Cancer Institute
    Harvard Medical School, Boston)

  • Myles Brown

    (Dana-Farber Cancer Institute
    Harvard Medical School, Boston
    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute)

  • John L. Rinn

    (Harvard University
    Broad Institute of Massachusetts Institute of Technology and Harvard
    Beth Israel Deaconess Medical Center)

  • Mary Gwo-Shu Lee

    (Dana-Farber Cancer Institute
    Harvard Medical School, Boston)

  • Yiwen Chen

    (University of Texas MD Anderson Cancer Center)

  • Philip W. Kantoff

    (Dana-Farber Cancer Institute
    Harvard Medical School, Boston
    Department of Medicine Memorial Sloan Kettering Cancer Center 1275 York Avenue)

  • X. Shirley Liu

    (Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute
    Dana-Farber Cancer Institute and Harvard School of Public Health)

Abstract

Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours. We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.

Suggested Citation

  • Zhou Du & Tong Sun & Ezgi Hacisuleyman & Teng Fei & Xiaodong Wang & Myles Brown & John L. Rinn & Mary Gwo-Shu Lee & Yiwen Chen & Philip W. Kantoff & X. Shirley Liu, 2016. "Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10982
    DOI: 10.1038/ncomms10982
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