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.