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.
Highlights
Mounting evidence suggests that long noncoding RNAs can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts
Our study suggests an important role of long noncoding RNAs (lncRNAs)-mediated sponge regulation in cancer and implied a therapeutical strategy of manipulating cancer gene function through modulating lncRNA-mediated sponge regulation
These results suggest that the regulation of PTEN by sp-lncRNAs is through the PTEN 30 untranslated region (30UTR)
Summary
Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. The human genome encodes around ten thousand lncRNA genes[1,2,3] and, similar to protein-coding genes (PCGs), some lncRNAs can mediate oncogenesis or tumour suppression and are, a potential new class of cancer therapeutic targets[4]. Despite this relevance to cancer, only a handful of lncRNAs have been functionally characterized. The pseudogenes of oncogenic PCGs, such as kirsten rat sarcoma viral oncogene homolog (KRAS), are miRNA sponges[12]
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