Latest @ CSI

Competing Endogenous RNA Networks: Tying the Essential Knots for Cancer Biology and Therapeutics (J Hematol Oncol, Mar 2015)

Avencia Sanchez-Mejias A1 and Yvonne Tay1, 2

1Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore

2Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore

Abstract

A recently discovered dimension of post-transcriptional gene regulation involves co-regulatory crosstalk between RNA transcripts, which compete for common pools of microRNA (miRNA) molecules. These competing endogenous RNAs (ceRNAs), or natural miRNA sponges, have an active role in regulating miRNA availability within the cell and form intertwined regulatory networks. Recent reports have implicated diverse RNA species including protein-coding messenger RNAs and non-coding RNAs as ceRNAs in human development and diseases including human cancer. In this review, we discuss the most recent discoveries that implicate natural miRNA decoys in human cancer biology, as well as exciting advances in the study of ceRNA networks and dynamics. The structure and topology of intricate genome-scale ceRNA networks can be predicted computationally, and their dynamic response to fluctuations in ceRNA and miRNA levels can be studied via mathematical modeling. Additionally, the development of new methods to quantitatively determine absolute expression levels of miRNA and ceRNA molecules have expanded the capacity to accurately study the efficiency of ceRNA crosstalk in diverse biological models. These major milestones are of critical importance to identify key components of ceRNA regulatory networks that could aid the development of new approaches to cancer diagnostics and oligonucleotide-based therapeutics.

YTay ceRNA 1

Fig. 1 Involvement of ceRNA-mediated regulation in human cancers. Schematic representation of a simplified ceRNA network with two transcripts and one miRNA (blue circle), and the different cancers for which ceRNA activity has been experimentally verified (orange circles).