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

Abstract

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’.

LncRNA‐ENST00000501520 promotes the proliferation of malignant‐transformed BEAS‐2B cells induced with coal tar pitch mediated by target genes

“…Present study showed that LncRNAs could form double strands with relevant miRNAs, which influenced the function of mRNAs by regulating miRNAs . It could also regulate the transcription of corresponding coding gene by binding with proteins in nuclear . In this study, the coexpression network analysis of ENST00000501520 was conducted by CNC, and 15 target genes were screened out.…”

“…27,28 It could also regulate the transcription of corresponding coding gene by binding with proteins in nuclear. 29 In this study, the coexpression network analysis of ENST00000501520 was conducted by CNC, and 15 target genes were screened out. When ENST00000501520 was interfered using siRNA, the mRNA expression of five genes (SBK1, CLTB, TAP2, RIPK2, and SOCS3) was changed significantly by qPCR.…”

The Promises and Challenges of Toxico-Epigenomics: Environmental Chemicals and Their Impacts on the Epigenome

“…Although these three modes of epigenetic regulation converge on a common cellular process (i.e., regulating gene expression), the mechanisms may act with different degrees of dynamic effects, strengths, and reversibility (Bintu et al 2016). Moreover, although they are often studied independently, it is becoming increasingly clear that there is extensive cross-talk between DNA methylation, histone modifications, and ncRNAs (Hanly et al 2018;Rose and Klose 2014;Vaissière et al 2008).…”

Fluctuations of Histone Chemical Modifications in Breast, Prostate, and Colorectal Cancer: An Implication of Phytochemicals as Defenders of Chromatin Equilibrium

“…Another way of HMTs posttranscriptional regulation represents a molecular cascade resulting in phosphorylation of enzymes (e.g., AKT-mediated phosphorylation of EZH2) and thus, in modulation of the catalytic activity of methyltransferases [93]. Importantly, regulatory processes mediated by ncRNA, including miRNA (miR-101) and lncRNA, suggest a linkage between levels of these RNA and the enzymatic activity of HMTs [94][95][96]. Histone methylation is a dominant modification responsible for chromatin remodeling mediated by numerous HMT enzymes.…”