Epigenetic modulations of noncoding RNA: a novel dimension of Cancer biology

Abstract

Empowered by recent advances of sequencing techniques, transcriptome-wide studies have characterized over 150 different types of post-transcriptional chemical modifications of RNA, ranging from methylations of single base to complex installing reactions catalyzed by coordinated actions of multiple modification enzymes. These modifications have been shown to regulate the function and fate of RNAs and further affecting various cellular events. However, the current understanding of their biological functions in human diseases, especially in cancers, is still limited. Once regarded as "junk" or "noise" of the transcriptome, noncoding RNA (ncRNA) has been proved to be involved in a plethora of cellular signaling pathways especially those regulating cancer initiation and progression. Accumulating evidence has demonstrated that ncRNAs manipulate multiple phenotypes of cancer cells including proliferation, metastasis and chemoresistance and may become promising biomarkers and targets for diagnosis and treatment of cancer. Importantly, recent studies have mapped plenty of modified residues in ncRNA transcripts, indicating the existence of epigenetic modulation of ncRNAs and the potential effects of RNA modulation on cancer progression. In this review, we briefly introduced the characteristics of several main epigenetic marks on ncRNAs and summarized their consecutive effects on cancer cells. We found that ncRNAs could act both as regulators and targets of epigenetic enzymes, which indicated a cross-regulating network in cancer cells and unveil a novel dimension of cancer biology. Moreover, by epitomizing the knowledge of RNA epigenetics, our work may pave the way for the design of patienttailored therapeutics of cancers.

RNA m6A Modification in Cancers: Molecular Mechanisms and Potential Clinical Applications

“…Moreover, how m 6 A RNA modification affects the functions of ncRNAs still remains unclear and ncRNAs have been confirmed having a close link with a wide variety of tumors. 15,191 carRNAs recently were found to have m 6 A modifications on them, which were deposited by METTL3, including repeat RNAs, promoter-associated RNAs, and enhancer RNAs. 52 Thus, the direct crosstalk between the m 6 A carRNA modifications and chromatin state opens a new door on how m 6 A carRNA modifications regulate transcription.…”

Cancer Epigenomics and Beyond: Advancing the Precision Oncology Paradigm

“…[102] Methylation of ncRNA on adenine and cytosine bases are increasingly recognized to be important in cancers. [103] Methylation and other covalent chemical modifications of noncoding and other classes of RNAs, termed ''epitranscriptomics,'' is emerging as an active area of cancer research made feasible by new chemical probing and sequencing techniques. [104,105] The RNAspecific enzymes that catalyze the chemical modification, the so-called epigenetic writers, readers, and erasers, are similar to those for DNA.…”

tRNA-derived RNA fragments in cancer: current status and future perspectives

“…In addition to protein-coding messenger RNAs (mRNAs), research over the past few decades has elucidated roles for non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and small non-coding RNAs (sncRNAs), in various biological processes. ncRNAs' involvement in complex mechanisms that play crucial roles in the development and progression of cancers [1][2][3][4] has been elucidated, thus challenging the previous views of these molecules as merely transcriptional "junk. "…”