摘要
The competitive endogenous RNA (ceRNA) hypothesis, which suggests a global regulatory mechanism operating through miRNA-mediated cross talks, has met with considerable skepticism. Quantitative analyses demonstrate that the absolute abundance of highly expressed miRNAs typically far exceeds that of sponging mRNAs, hence ceRNA-based regulation is unlikely under physiological conditions. However, whether the highly expressed miRNAs dominate the global ceRNA network or not has not been analyzed. Here we systematically examined miRNAs and miRNA-binding mRNAs across a large cohort of tissues. Intriguingly, while a few highly-expressed miRNAs (himiRs) dominate the miRNA landscape in all analyzed tissues, there are many more miRNAs expressed at intermediate levels (med-miRs), and ceRNA interactions are possible among medmiR-associated mRNAs. Critically, the number of med-miR-associated mRNAs is substantially higher than hi-miR-associated mRNAs. Consequently, the med-miR-mediated ceRNA network is not significantly inhibited by hi-miRs and are operational despite the presence of highly expressed miRNAs. Taken together, our analyses demonstrated that functional ceRNA networks are evolved to perform distinct functions from hi-miRs, and are likely of physiological significance.
