The interplay between m6A RNA methylation and noncoding RNA in cancer

Abstract

N6-methyladenosine (m6A) methylation, one of the most common RNA modifications, has been reported to execute important functions that affect normal life activities and diseases. Most studies have suggested that m6A modification can affect the complexity of cancer progression by regulating biological functions related to cancer. M6A modification of noncoding RNAs regulates the cleavage, transport, stability, and degradation of noncoding RNAs themselves. It also regulates cell proliferation and metastasis, stem cell differentiation, and homeostasis in cancer by affecting the biological function of cells. Interestingly, noncoding RNAs also play significant roles in regulating these m6A modifications. Additionally, it is becoming increasingly clear that m6A and noncoding RNAs potentially contribute to the clinical application of cancer treatment. In this review, we summarize the effect of the interactions between m6A modifications and noncoding RNAs on the biological functions involved in cancer progression. In particular, we discuss the role of m6A and noncoding RNAs as possible potential biomarkers and therapeutic targets in the treatment of cancers.

RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

“…There are various RBPs, like IGF2BP and the family of YTH domain-containing proteins, that, so to say, read m6A modifications, selectively bind to m6A-modified sites, and subsequently regulate RNA stability, alternative splicing, transport, and translation [109,110]. Hence, the proteins responsible for generating m6A modifications, the ones reading them, like IGF2BP1, and those removing them, namely fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5), altogether impact not only mRNAs but also lncRNAs on the post-transcriptional level [109][110][111]. As this includes oncogenes and tumor suppressors alike, aberrant levels of the m6A modification are linked to tumorigenesis and cancer progression, and have thus received quite some interest in research lately [109][110][111].…”

“…Hence, the proteins responsible for generating m6A modifications, the ones reading them, like IGF2BP1, and those removing them, namely fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5), altogether impact not only mRNAs but also lncRNAs on the post-transcriptional level [109][110][111]. As this includes oncogenes and tumor suppressors alike, aberrant levels of the m6A modification are linked to tumorigenesis and cancer progression, and have thus received quite some interest in research lately [109][110][111]. For example, in hepatocellular carcinoma (HCC) the methyltransferase METTL3 is elevated and contributes to tumor progression by generating higher levels of m6A modification in the suppressor of cytokine signaling 2 (SOCS2) mRNA which results in its increased degradation mediated by the YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2) [112].…”

An Emerging Role of m6A in Memory: A Case for Translational Priming

“…Since the initial in vitro characterization of m6A in 1974 [ 3 ], little progress was made toward understanding its function until recent work reignited an interest in this RNA modification. Although m6A has been implicated in regulating non-coding RNA [ 4 ], its role in mRNA regulation is better understood and as such, m6A in mRNA will be the focus of the current review. Emerging consensus is that m6A can influence nearly every fate of the tagged mRNA across complex systems [ 4 ], including the brain [ 5 ], but that precise functions of m6A depend on the spatial location it occupies within the mRNA, as well as the specific reader proteins that recognize m6A.…”

The prognostic value of METTL3 in cancer patients: a meta-analysis

“…The occurrence of m6A modi cation is encoded by methyltransferase complex. It can add, remove and read m6A sites respectively through the writer, eraser and reader [12][13][14][15].New evidences showed that by controlling the expression of oncogenes or tumor suppressor genes, m6A modi cation could regulate the occurrence, differentiation and metastasis of tumors [14,16,17]. METTL3 (methyltransferase like 3) is one of N6 methyladenosylmethy transferases, which plays an important role in mRNA pre-splicing, 3 '-terminal processing and translation regulation [18][19][20][21].According to recent studies, METTL3 can also in uence the tumorigenesis and growth of tumor by regulating the m6A modi cation [21][22][23].This mechanism has been found in a variety of tumor tissues [24][25][26].…”