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.

The functions and unique features of long intergenic non-coding RNA

“…The levels of linc-RoR decrease during differentiation, and miR-145 is released and promotes the degradation of its pluripotency-promoting targets 106 . Similarly, the lincRNA TUG1, which associates with PRC2 in the nucleus, acts as a sponge of PTEN-targeting mi RNAs in the cytoplasm 22 , thereby adopting compartment-specific roles.…”

Mammalian microRNAs and long noncoding RNAs in the host-bacterial pathogen crosstalk

“…Thus, a complex regulatory network is at play in the host cell to tightly modulate gene expression. This type of interplay might be involved in host response against bacterial infection, as recently shown for cancer [106]. Given the arising data on the ability of regulatory RNAs produced by pathogens to regulate host gene expression and also the possible regulatory function of cellular RNAs on the pathogen, the role of RNA in the host-pathogen crosstalk might be even more sophisticated than previously anticipated (Fig.…”

Integrative analysis of competing endogenous RNA networks reveals the functional lncRNAs in heart failure

“…This novel transcript has been demonstrated to play important roles in wide range of biological processes 40. Dysfunction of lncRNAs could lead to the changes in various complicated disease phenotypes, from cancer to cardiovascular disease 41, 42. It has become a necessary way to investigate the underlying mechanisms of lncRNAs in heart failure for clinical therapy.…”