Functions of RNA N6-methyladenosine modification in cancer progression

Chen, Bing; Li, Ya; Song, Ruifeng; Xue, Chen; Xu, Feng

doi:10.1007/s11033-018-4471-6

Cited by 29 publications

(28 citation statements)

References 106 publications

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“…S5I). In this study, we suggested that the motifs "GA (m6A) CA" (site 2 and site 3) can be read by YTHDF1 1,70 and that the motifs "GG (m6A) CU" (site 4) and "UG (m6A) CU" (site 5) can be read by YTHDF2 2,70,71 . These results were consistent with previous studies showing that multiple mRNA transcripts containing the "GRAC" (R is G or A) motif can be read by YTHDF1, while the "G (m6A) CU" motif has the strongest affinity for YTHDF2 in the YTH family 1,2,72 .…”

Section: Discussionmentioning

confidence: 86%

A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR

Yao

et al. 2020

Cell Death Dis

110

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Previous studies have revealed the critical roles of the N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) in cancers, but the relationship between the oncogenic role of the lncRNA THOR (a representative of cancer/testis lncRNAs) and m6A modification remains unclear. Here, we show that the internal m6A modification of the lncRNA THOR via an m6A-reader-dependent modality regulates the proliferation of cancer cells. Our findings demonstrated that the loss of the lncRNA THOR inhibits the proliferation, migration, and invasion of cancer cells in vitro and in vivo. In addition, m6A is highly enriched on lncRNA THOR transcripts, which contain GA (m6A) CA, GG (m6A) CU, and UG (m6A) CU sequence motifs. RIP-qRT-PCR and RNA pull-down assay results revealed that the specific m6A readers YTHDF1 and YTHDF2 can read the m6A motifs and regulate the stability of the lncRNA THOR (stabilization and decay). These m6A-dependent RNA-protein interactions can maintain the oncogenic role of the lncRNA THOR. Collectively, these findings highlight the critical role of the m6A modification in oncogenic lncRNA THOR and reveal a novel long non-coding RNA regulatory mechanism, providing a new way to explore RNA epigenetic regulatory patterns in the future. Recently, the new field of "RNA epigenetics" has been booming 14,15 , and N6-methyladenosine (m6A) has been identified as a post-transcriptional regulatory mark in multiple RNA species, including messenger RNAs (mRNAs) 1,2,16 , transfer RNAs (tRNAs) 3,4,17-20 , ribosomal RNAs (rRNAs) 21 , small nuclear RNA 22 , small non-coding RNAs (sncRNAs) 23 , and lncRNAs 16,24. It has been reported that the m6A RNA modification is conferred by methyltransferases (writers), such as methyltransferaselike 3 (METTL3), forming the catalytic core of the m6A methyltransferase complex 25-28. In addition, the biological function of m6A is mediated through the recognition of the m6A site by m6A "readers" 1,29,30 , such as the YT521-B homology (YTH) family, including YTH domain

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Section: Discussionmentioning

confidence: 86%

A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR

Yao

et al. 2020

Cell Death Dis

110

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“…Epigenetics has become a hot topic in scientific research nowadays [37,163]. The m6A methylation participates in regulation of cancer malignant phenotype by HCC: human hepatocellular carcinoma; AML: acute myeloid leukemia controlling the expression of cancer-related genes [164][165][166]. Abnormal level of m6A methylation contributes to tumor pathogenesis and progression.…”

Section: Resultsmentioning

confidence: 99%

Functions of N6-methyladenosine and its role in cancer

et al. 2019

Mol Cancer

974

816

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N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which is the most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests that m6A modulates gene expression, thereby regulating cellular processes ranging from cell self-renewal, differentiation, invasion and apoptosis. M6A is installed by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which regulate of RNA metabolism including translation, splicing, export, degradation and microRNA processing. Alteration of m6A levels participates in cancer pathogenesis and development via regulating expression of tumor-related genes like BRD4, MYC, SOCS2 and EGFR. In this review, we elaborate on recent advances in research of m6A enzymes. We also highlight the underlying mechanism of m6A in cancer pathogenesis and progression. Finally, we review corresponding potential targets in cancer therapy.

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“…In addition, a variety of studies have shown that m 6 A modification plays promotive or inhibitory roles in various cancers (7). Upon alteration of m 6 A regulatory genes or a change in the expression of proteins related to m 6 A methylation, m 6 A impacts the initiation and progression of various human malignancies through diverse mechanisms and is involved in different biological processes, including viral infection (8), immune responses, tissue renewal (8)(9)(10), stem cell differentiation, and motility (11), and therefore exerts a profound impact on cancer development (8). m 6 A deposition is accomplished by a methyltransferase (MTase) complex referred to as "writers."…”

Section: Introductionmentioning

confidence: 99%

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

et al. 2019

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Methyltransferase-like 3 (METTL3), a predominantly catalytic enzyme in the N 6 -methyladenosine (m 6 A) methyltransferase system, is dysregulated and plays a dual role (oncogene or tumor suppressor) in different human cancers. The expression and pro-or anticancer role of METTL3 in different cancers remain controversial. METTL3 is implicated in many aspects of tumor progression, including tumorigenesis, proliferation, invasion, migration, cell cycle, differentiation, and viability. Most underlying mechanisms involve multiple signaling pathways that rely on m 6 A-dependent modification. However, METTL3 can also modulate the cancer process by directly promoting the translation of oncogenes via interaction with the translation initiation machinery through recruitment of eukaryotic translation initiation factor 3 subunit h (eIF3h). In this review, we summarized the current evidence on METTL3 in diverse human malignancies and its potential as a prognostic/ therapeutic target.

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Functions of RNA N6-methyladenosine modification in cancer progression

Cited by 29 publications

References 106 publications

A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR

A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR

Functions of N6-methyladenosine and its role in cancer

Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers

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