RNA binding protein-mediated competing endogenous RNA mechanism in cancer

It is evidently now that long non-coding RNAs (lncRNAs) play vital roles in development of cancer through versatile mechanisms. Of importance, lncRNAs play such a regulatory role often through interacting with their partners, including DNAs, RNAs or proteins. Thus, it is critical to dissect the interaction of lncRNAs with their binding partners in order to fully understand the mechanism underlying the lncRNA-mediated gene expression. In this review, we present the current state of knowledge implicating lncRNAs in gene regulation through RNA binding proteins (RBPs). We first describe briefly the known functions of lncRNAs and then introduce RBPs related to lncRNA function. We also touch on DNA-RNA binding proteins (DRBPs) as a special group of RBPs and how lncRNAs interact with DRBPs, leading to gene expression. Next, we provide a few examples such as RBP-mediated RNA stability, alternative splicing and RNA methylation to highlight the importance of lncRNA-RBP interaction. Finally, we compare RPBs with microRNAs for their functions in gene regulation. It is well known that microRNAs can silence multiple targets including coding genes and non-coding genes through microRNA response elements (MREs); similarly, RBPs can regulate targeted genes through RBP binding sites (RBP-BSs). However, RBPs often carry multiple RNA binding domains and they are also capable of interacting with other proteins or RNAs, forming a "competing endogenous RNA (ceRNA)" network. With involvement of lncRNAs, this regulatory system becomes even more complex and powerful. Thus, the detailed dissection of the lncRNA-RBP interaction will provide new insight into this gene regulatory system.