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

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

doi:10.1038/ncomms10982

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

Nat Commun. 2016 Mar 15:7:10982. doi: 10.1038/ncomms10982.

Authors

Zhou Du^{1

2}, Tong Sun^{3

4

5}, Ezgi Hacisuleyman^{6

7

8}, Teng Fei^{3

4

9}, Xiaodong Wang^{3

4}, Myles Brown^{3

4

9}, John L Rinn^{7

8

10}, Mary Gwo-Shu Lee^{3

4}, Yiwen Chen¹¹, Philip W Kantoff^{3

4

12}, X Shirley Liu^{9

13}

Affiliations

¹ Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Shanghai 200433, China.
² Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
⁴ Harvard Medical School, Boston, Massachusetts 02215, USA.
⁵ Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
⁶ Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
⁷ Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
⁸ Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.
⁹ Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
¹⁰ Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
¹¹ Department of Bioinformatics and Computational Biology, Division of Quantitative Sciences, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
¹² Department of Medicine Memorial Sloan Kettering Cancer Center 1275 York Avenue, New York, New York 10065, USA.
¹³ Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02215, USA.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / genetics*
Blotting, Western
Cell Fractionation
Cell Proliferation
Chromatin Immunoprecipitation
Gene Expression Regulation, Neoplastic / genetics*
Gene Regulatory Networks
HCT116 Cells
Humans
In Situ Hybridization, Fluorescence
Male
MicroRNAs
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / metabolism
Polycomb Repressive Complex 2
Prostatic Neoplasms / genetics*
RNA Transport / genetics
RNA, Long Noncoding / genetics
RNA, Long Noncoding / physiology*
Reverse Transcriptase Polymerase Chain Reaction

Substances

MicroRNAs
RNA, Long Noncoding
TUG1 long noncoding RNA, human
Polycomb Repressive Complex 2
PTEN Phosphohydrolase
PTEN protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding