Long noncoding RNA networks of suppression

Of the approximately 10,000 long noncoding (lnc) RNAs encoded in the human genome, the functions of only a few have been characterized. 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, researchers from the Dana-Farber Cancer Institute 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. They 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. These 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.

Computational prediction of sp-lncRNA regulation in prostate cancer


(a) The mechanism by which RNAs that are targeted by the same miRNA cross-regulate the expression of each other and the main features of the computational strategy for predicting sp-lncRNA. (b) The computational strategy of predicting lncRNA-mediated sponge regulation of protein-coding driver genes in prostate cancer. (c) A citros plot showing the computationally predicted sp-lncRNA network. The nodes represent individual genes and the edges represent the predicted regulation between sp-lncRNA and the corresponding protein-coding driver gene. FDR, false discovery rate.

Du Z, Sun T, Hacisuleyman E, Fei T, Wang X, Brown M, Rinn JL, Lee MG, Chen Y, Kantoff PW, Liu XS. (2016) Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer. Nat Commun 7:10982. [article]

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