ceRNA cross-talk in cancer: when ce-bling rivalries go awry.
The cancer transcriptome is characterized by aberrant expression of both protein-coding and noncoding transcripts. Similar to mRNAs, a significant portion of the noncoding transcriptome, including long noncoding RNAs and pseudogenes, harbors microRNA (miRNA)-response elements (MRE). The recent discovery of competitive endogenous RNAs (ceRNA), natural decoys that compete for a common pool of miRNAs, provides a framework to systematically functionalize MRE-harboring noncoding RNAs and integrate them with the protein-coding RNA dimension in complex ceRNA networks. Functional interactions in ceRNA networks aid in coordinating a number of biologic processes and, when perturbed, contribute to disease pathogenesis. In this review, we discuss recent discoveries that implicate natural miRNA decoys in the development of cancer.


CONCLUSIONS
Cross-talk between ceRNAs through shared miRNAs represents a novel layer of gene regulation that plays important roles in the physiology and development of diseases such as cancer. As cross-talk can be predicted on the basis of the overlap of miRNA-binding sites, we are now one step closer to a complete functionalization of the human transcriptome, especially the noncoding space.
Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Florian A
FA
Karreth
Pier Paolo
PP
Pandolfi
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011544:Pseudogenes; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D059467:Transcriptome / Q000235:genetics*
D020413:3' Untranslated Regions; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated