Role of m6A writers, erasers and readers in cancer

Fang, Zhen; Mei, Wentong; Qu, Chang; Lu, Jiongdi; Shang, Liang; Cao, Feng; Li, Fēi

doi:10.1186/s40164-022-00298-7

Cited by 101 publications

(68 citation statements)

References 318 publications

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“…RNA modification is an essential post-transcriptional mechanism that rapidly mediates RNA and protein levels without affecting DNA or histones. The regulation and function of the RNA methylation m 6 A in human malignancies have been studied most intensively, revealing that m 6 A affects various tumor processes [ 36 , 37 ], such as proliferation [ 20 , 21 ], stemness [ 38 ], and metastasis formation [ 39 ]. Besides, m 5 C mediates mRNA stability and translation, exerting powerful effects in multiple tumor types [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Low expression of PEBP1P2 promotes metastasis of clear cell renal cell carcinoma by post-transcriptional regulation of PEBP1 and KLF13 mRNA

et al. 2022

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Background Pseudogenes play an essential role in tumor occurrence and progression. However, the functions and mechanisms of pseudogenes in clear cell renal cell carcinoma (ccRCC) remain largely elusive. Methods We quantified PEBP1P2 expression in ccRCC tissues and cells using fluorescence in situ hybridization and real-time PCR. Besides, we evaluated the role of PEBP1P2 in ccRCC using a lung metastasis model and a transwell assay. Finally, we documented the interactions between PEBP1P2, PEBP1, and KLF13 by performing luciferase, RNA immunoprecipitation, RNA pulldown, and targeted RNA demethylation assays. Results Low PEBP1P2 expression correlates significantly with advanced stages and poor prognosis in ccRCC patients. Besides, PEBP1P2 overexpression inhibits ccRCC metastasis formation in vivo and in vitro. Interestingly, PEBP1P2 directly interacted with 5-methylcytosine (m5C)-containing PEBP1 mRNA and recruited the YBX1/ELAVL1 complex, stabilizing PEBP1 mRNA. In addition, PEBP1P2 increased KLF13 mRNA levels by acting as a sponge for miR-296, miR-616, and miR-3194. Conclusions PEBP1P2 inhibits ccRCC metastasis formation and regulates both PEBP1 and KLF13. Therefore, molecular therapies targeting PEBP1P2 might be an effective treatment strategy against ccRCC and other cancers with low PEBP1P2 levels.

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Section: Discussionmentioning

confidence: 99%

Low expression of PEBP1P2 promotes metastasis of clear cell renal cell carcinoma by post-transcriptional regulation of PEBP1 and KLF13 mRNA

et al. 2022

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“…Given the potential significance of RNA m 6 A modification in human health and disease, efforts of the past few years have focused on the identification of regulators of this modification. m 6 A methylation is introduced by methyltransferases and can be removed either passively, via the degradation of the modified RNA, or actively, by erasers such as the dioxygenases FTO or ALKBH5 [ 7 , 17 , 18 , 19 ]. Resembling the function ascribed to histone modifications, m 6 A modification can cause a structural switch and/or act as a signal for the recruitment of downstream effectors that influence the fate of the target mRNA [ 20 , 21 , 22 , 23 , 24 ].…”

Section: M 6 a Rna Methylationmentioning

confidence: 99%

“…Some readers, such as YTH-domain-containing family members, can bind directly to m 6 A methylated RNAs. Alternatively, the modulation of the secondary RNA structure can expose or mask RNA-binding motifs recognized by reader proteins, leading to an m 6 A-dependent regulation of RNA maturation and gene expression [ 7 , 17 , 18 , 19 ].…”

Section: M 6 a Rna Methylationmentioning

confidence: 99%

The Role of the m6A RNA Methyltransferase METTL16 in Gene Expression and SAM Homeostasis

Mermoud

2022

Genes

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The RNA methylation of adenosine at the N6-position (m6A) has attracted significant attention because of its abundance and dynamic nature. It accounts for more than 80% of all RNA modifications present in bacteria and eukaryotes and regulates crucial aspects of RNA biology and gene expression in numerous biological processes. The majority of m6A found in mammals is deposited by a multicomponent complex formed between methyltransferase-like (METTL) proteins METTL3 and METTL14. In the last few years, the list of m6A writers has grown, resulting in an expansion of our understanding of the importance of m6A and the methylation machinery. The characterization of the less familiar family member METTL16 has uncovered a new function of the m6A methylation apparatus, namely the fine-tuning of the cellular levels of the major methyl donor S-adenosylmethionine (SAM). METTL16 achieves this by adjusting the levels of the enzyme that synthesizes SAM in direct response to fluctuations in the SAM availability. This review summarizes recent progress made in understanding how METTL16 can sense and relay metabolic information and considers the wider implications. A brief survey highlights similarities and differences between METTL16 and the better-known METTL3/14 complex, followed by a discussion of the target specificity, modes of action and potential roles of METTL16.

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“…It suggested that the m 6 A modi cation might also play a crucial regulatory role in the development and progression of human cancers. Along with the in-depth study, 23 regulatory genes related to m 6 A modi cation were known (8 Writers, 13 Readers and 2 Erasers) were identi ed thoroughly [9,10]. More and more studies have demonstrated that these 23 m 6 A regulators closely participated in the cancer progression.…”

Section: Introductionmentioning

confidence: 99%

RNA methylation patterns mediated by m 6 A regulators are involved in the regulation of immune microenvironment in hepatocellular carcinoma

Gao

Liu

Zhang

et al. 2023

Preprint

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Background: It has been reported that epigenetic regulation is emerging as a new regulatory pattern, especially for RNA N6-methyladenosine (m6A) modifications. It has been reported to play an important biological function in immunity. However, the role of m6A on the immune microenvironment in hepatocellular carcinoma (HCC) remains unclear. In this study, we systematically evaluated the RNA modification patterns mediated by 23 m6A modulators in HCC samples using the TCGA database. Methods and results: The effects of m6A modification on the characteristics of immune microenvironment gene were investigated. Meanwhile, we characterized m6A phenotype-related immune genes. Our study further identified two distinct patterns of RNA modification mediated by 23 m6A modulators. They have different immune cell abundances, immune responses, and HLA genes. Conclusion: In a word, our findings suggest that m6A modification plays a crucial role in regulating the immune microenvironment in HCC, providing a guiding significance in the selection of immunotherapy or target for treating HCC.

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Role of m6A writers, erasers and readers in cancer

Cited by 101 publications

References 318 publications

Low expression of PEBP1P2 promotes metastasis of clear cell renal cell carcinoma by post-transcriptional regulation of PEBP1 and KLF13 mRNA

Low expression of PEBP1P2 promotes metastasis of clear cell renal cell carcinoma by post-transcriptional regulation of PEBP1 and KLF13 mRNA

The Role of the m6A RNA Methyltransferase METTL16 in Gene Expression and SAM Homeostasis

RNA methylation patterns mediated by m 6 A regulators are involved in the regulation of immune microenvironment in hepatocellular carcinoma

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