Interplay between long non-coding RNAs and epigenetic machinery: emerging targets in cancer?

Of the diverse array of putative molecular and biological functions assigned to long non-coding RNAs (lncRNAs), one attractive perspective in epigenetic research has been the hypothesis that lncRNAs directly interact with the proteins involved in the modulation of chromatin conformation. Indeed, epigenetic modifiers are among the most frequent protein partners of lncRNAs that have been identified to date, of which histone methyltransferases and protein members of the Polycomb Repressive Complex PRC2 have received considerable attention. This review is focused on how lncRNAs interface with epigenetic factors to shape the outcomes of crucial biological processes such as regulation of gene transcription, modulation of nuclear architecture, X inactivation in females and pre-mRNA splicing. Because of our increasing knowledge of their role in development and cellular differentiation, more research is beginning to be done into the deregulation of lncRNAs in human disorders. Focusing on cancer, we describe some key examples of disease-focused lncRNA studies. This knowledge has significantly contributed to our ever-improving understanding of how lncRNAs interact with epigenetic factors of human disease, and has also provided a plethora of much-needed novel prognostic biomarker candidates or potential therapeutic targets. Finally, current limitations and perspectives on lncRNA research are discussed here. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.