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

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

Bioinformatics & Computational Biology

Research output: Contribution to journal › Article › peer-review

250 Scopus citations

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.

Original language	English (US)
Article number	10982
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10982
State	Published - Mar 15 2016

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

MD Anderson CCSG core facilities

Bioinformatics Shared Resource

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10.1038/ncomms10982

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@article{4c4b9200b5f3438f9721e72505a0b273,

title = "Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer",

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.",

author = "Zhou Du and Tong Sun and Ezgi Hacisuleyman and Teng Fei and Xiaodong Wang and Myles Brown and Rinn, {John L.} and Lee, {Mary Gwo Shu} and Yiwen Chen and Kantoff, {Philip W.} and Liu, {X. Shirley}",

note = "Funding Information: We thank Dr Bert Vogelstein for sharing the wild-type HCT116 and HCT116 Dicerex5 cells, Dr Marc Beal for his help with RNA-FISH probe-design and, Dr Xuerui Yang and Dr Andrea Califano for sharing the luciferase-PTEN-3′UTR reporter construct. This work was partially funded by National Natural Science Foundation of China 31329003 to X.S.L., 2012M520923 to D.Z., NIH/NCI U01CA180980 to X.S.L., NIH/NCI R00CA175290, University of Texas Rising STARs award, University of Texas at MD Anderson Cancer Center start-up fund and Texas CPRIT grant RR140071 to Y.C. This work was also supported in part by US National Cancer Institute (NCI; MD Anderson TCGA Genome Data Analysis Center) grant number CA143883, the Cancer Prevention Research Institute of Texas (CPRIT) grant number RP130397, the Mary K. Chapman Foundation, the Michael and Susan Dell Foundation (honoring Lorraine Dell) and MD Anderson Cancer Center Support Grant P30 CA016672 (the Bioinformatics Shared Resource). J.L.R. is the Alvin and Esta Star Associate Professor and is supported by NIH/NIEHS R01ES020260.",

year = "2016",

month = mar,

day = "15",

doi = "10.1038/ncomms10982",

language = "English (US)",

volume = "7",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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TY - JOUR

T1 - Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer

AU - Du, Zhou

AU - Sun, Tong

AU - Hacisuleyman, Ezgi

AU - Fei, Teng

AU - Wang, Xiaodong

AU - Brown, Myles

AU - Rinn, John L.

AU - Lee, Mary Gwo Shu

AU - Chen, Yiwen

AU - Kantoff, Philip W.

AU - Liu, X. Shirley

N1 - Funding Information: We thank Dr Bert Vogelstein for sharing the wild-type HCT116 and HCT116 Dicerex5 cells, Dr Marc Beal for his help with RNA-FISH probe-design and, Dr Xuerui Yang and Dr Andrea Califano for sharing the luciferase-PTEN-3′UTR reporter construct. This work was partially funded by National Natural Science Foundation of China 31329003 to X.S.L., 2012M520923 to D.Z., NIH/NCI U01CA180980 to X.S.L., NIH/NCI R00CA175290, University of Texas Rising STARs award, University of Texas at MD Anderson Cancer Center start-up fund and Texas CPRIT grant RR140071 to Y.C. This work was also supported in part by US National Cancer Institute (NCI; MD Anderson TCGA Genome Data Analysis Center) grant number CA143883, the Cancer Prevention Research Institute of Texas (CPRIT) grant number RP130397, the Mary K. Chapman Foundation, the Michael and Susan Dell Foundation (honoring Lorraine Dell) and MD Anderson Cancer Center Support Grant P30 CA016672 (the Bioinformatics Shared Resource). J.L.R. is the Alvin and Esta Star Associate Professor and is supported by NIH/NIEHS R01ES020260.

PY - 2016/3/15

Y1 - 2016/3/15

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms10982

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JO - Nature communications

JF - Nature communications

M1 - 10982

ER -

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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