The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer

Abstract

Most of our transcribed RNAs are represented by non-coding sequences. Long non-coding RNAs (lncRNAs) are transcripts with no or very limited protein coding ability and a length >200nt. They can be epigenetically modified. N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G) and 2’-O-methylation (Nm) are some of the lncRNAs epigenetic modifications. The epigenetic modifications of RNA are controlled by three classes of enzymes, each playing a role in a specific phase of the modification. These enzymes are defined as “writers”, “readers” and “erasers”. m6A and m5C are the most studied epigenetic modifications in RNA. These modifications alter the structure and properties, thus modulating the functions and interactions of lncRNAs. The aberrant expression of several lncRNAs is linked to the development of a variety of cancers and the epigenetic signatures of m6A- or m5C-related lncRNAs are increasingly recognized as potential biomarkers of prognosis, predictors of disease stage and overall survival. In the present manuscript, the most up to date literature is reviewed with the focus on m6A and m5C modifications of lncRNAs and their significance in cancer.

m6A modified lncRNA WAKMAR2 induces intestinal inflammation through an allele-specific RNA methylation dependent splicing mechanism

“…In addition, our ndings support the idea that the expression of longWAKMAR2 is also in uenced by m 6 A methylation, since we observed increased methylation levels in WAKMAR2 harboring the IBD risk allele, as well as an induction of overall methylation, in response to in ammation. This is consistent with previous research in which it has been shown that m 6 A methylation undergoes alterations in IBD (3) and can effectively regulate the expression and function of lncRNAs (17,(32)(33)(34).…”

5-Methylcytosine-related lncRNAs: predicting prognosis and identifying hot and cold tumor subtypes in head and neck squamous cell carcinoma

“…Multiple studies have determined lncRNAs can be regulated by m 5 C-related to participate in the biological process of tumors by regulating of RNA localization, stability, and transcription efficiency [ 28 ]. Referring to the summarized list reviewed by Cusenza et al, a large number of lncRNAs have been verified as signatures modified by m 5 C in malignancies, especially for squamous cell neoplasms [ 29 ]. For HNSCC patients, a reliable signature for prognostic prediction and immune infiltration assessment is necessary to develop an individual and precise treatment [ 3 ].…”

Nanotherapeutic approaches for delivery of long non-coding RNAs: an updated review with emphasis on cancer

“…For example, the lncRNA HOTAIR interacts with the PRC2 to promote the trimethylation of H3K27me3, inhibiting target gene transcription. 24,25 It is believed that lncRNAs regulate downstream gene transcription and influence specific signaling pathways when different stimulating conditions are applied. In additional, the lncRNA is used as a decoy because after it is translated, it directly binds to some protein molecules, such as proteins involved in chromosome folding or transcription regulators, and interferes with their functions.…”