Insights into the role of long non-coding RNAs in DNA methylation mediated transcriptional regulation

Abstract

DNA methylation is one of the most important epigenetic mechanisms that governing regulation of gene expression, aberrant DNA methylation patterns are strongly associated with human malignancies. Long non-coding RNAs (lncRNAs) have being discovered as a significant regulator on gene expression at the epigenetic level. Emerging evidences have indicated the intricate regulatory effects between lncRNAs and DNA methylation. On one hand, transcription of lncRNAs are controlled by the promoter methylation, which is similar to protein coding genes, on the other hand, lncRNA could interact with enzymes involved in DNA methylation to affect the methylation pattern of downstream genes, thus regulating their expression. In addition, circular RNAs (circRNAs) being an important class of noncoding RNA are also found to participate in this complex regulatory network. In this review, we summarize recent research progress on this crosstalk between lncRNA, circRNA, and DNA methylation as well as their potential functions in complex diseases including cancer. This work reveals a hidden layer for gene transcriptional regulation and enhances our understanding for epigenetics regarding detailed mechanisms on lncRNA regulatory function in human cancers.

LncRNA CRNDE is downregulated and associated with poor prognostic markers in chronic lymphocytic leukemia

“…On one side, transcription of lncRNAs is regulated by promoter methylation, on the other side, lncRNAs have an important role in DNA methylation by interacting with certain enzymes and so influencing downstream genes methylation, thus controlling their expression. 25 Interestingly Our findings might be explained in the context of the study conducted by Ni et al 28 They reported that CRNDE overexpression had an inhibiting effect on proliferation and had a promoting effect on This study has two main limitations. First, the small number of participants, so further validation studies on a larger number of patients are required to support our preliminary results.…”

“…In this regard, emerging evidence has revealed a substantial regulatory connection between DNA methylation and lncRNAs. On one side, transcription of lncRNAs is regulated by promoter methylation, on the other side, lncRNAs have an important role in DNA methylation by interacting with certain enzymes and so influencing downstream genes methylation, thus controlling their expression 25 …”

Non‐coding RNAs and colitis‐associated cancer: Mechanisms and clinical applications

“… 60 More interestingly, emerging evidence also suggests that DNA methylation of non‐coding RNA promoters can be one of the main mechanisms by which RNA expressions are regulated. 61 For instance, DNA methylation‐associated silencing of miR‐486‐5p could significantly promote the CRC development by activating the pleomorphic adenoma gene‐like 2/insulin‐like growth factor‐2/β‐catenin signalling pathway. 62 lncRNA‐SLCO4A1‐AS1 was commonly up‐regulated in CRC samples and acted as an oncogenic molecule in CRC patients by mediating a Hsp90/Cdk2/c‐Myc axis.…”

“…In the past decades, epigenetic modifications, including non‐coding RNAs, DNA methylation and chromatin modifications, have attracted more attentions as they can regulate gene expressions without altering the DNA sequence 60 . More interestingly, emerging evidence also suggests that DNA methylation of non‐coding RNA promoters can be one of the main mechanisms by which RNA expressions are regulated 61 . For instance, DNA methylation‐associated silencing of miR‐486‐5p could significantly promote the CRC development by activating the pleomorphic adenoma gene‐like 2/insulin‐like growth factor‐2/β‐catenin signalling pathway 62 .…”

lncRNAs-EZH2 interaction as promising therapeutic target in cutaneous melanoma

“…Many nuclear lncRNAs interact with chromatin regulators. Approximately 30% of lncRNAs have been associated with distinct chromatin regulatory complexes which include chromatin readers (chromobox proteins and transcription factors), writers (methyltransferases and acetyltransferases) and erasers (demethylases and deacetylases) ( Guttman et al, 2011 ; Yang et al, 2022 ). lncRNAs recruit histone modifying complexes to chromatin and subsequently targeted loci are either activated or silenced, depending on the specific histone mark.…”