m6A-binding proteins: the emerging crucial performers in epigenetics

Zhao, Yuechao; Shi, Yuanfei; Shen, Hangyan; Xie, Wanzhuo

doi:10.1186/s13045-020-00872-8

Cited by 212 publications

(211 citation statements)

References 120 publications

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“…The m 6 A modification has become a hot research topic in RNA modification–mediated epigenetic regulation, which was associated with the expression of gene and disease development, including cancer ( 33 , 34 ). The m 6 A modification is dynamically regulated via the methyltransferases and demethylases ( 12 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, the m 6 A “readers” could recognize m 6 A-modified sites and regulate RNA function. Recent studies have shown that m 6 A modification and its regulators play an important role in various cancers ( 33 ). Previous study has systematically characterized the molecular alterations and clinical relevance of 20 m 6 A RNA regulators across 33 cancer types, and they found that m 6 A regulators were found to be potentially useful for prognostic stratification and identified IGF2BP3 as a potential oncogene across multiple cancer types ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

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m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

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N6-methyladenosine (m 6 A) modification is the most abundant modification on eukaryotic RNA. In recent years, lots of studies have reported that m 6 A modification and m 6 A RNA methylation regulators were involved in cancer progression. However, the m 6 A level and its regulators in esophageal cancer (ESCA) remain poorly understood. In this study, we analyzed the expression of m 6 A regulators using The Cancer Genome Atlas data and found 14 of 19 m 6 A regulators are significantly increased in ESCA samples. Then we performed a univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) Cox regression model to investigate the prognostic role of m 6 A regulators in ESCA, and the results indicated that a two-gene prognostic signature including ALKBH5 and HNRNPA2B1 could predict overall survival of ESCA patients. Moreover, HNRNPA2B1 is higher expressed in high-risk scores subtype of ESCA, indicating that HNRNPA2B1 may be involved in ESCA development. Subsequently, we confirmed that the level of m 6 A and HNRNPA2B1 was significantly increased in ESCA. We also found that HNRNPA2B1 expression positively correlated with tumor diameter and lymphatic metastasis of ESCA. Moreover, functional study showed that knockdown of HNRNPA2B1 inhibited the proliferation, migration, and invasion of ESCA. Mechanistically, we found that knockdown of HNRNPA2B1 inhibited the expression of de novo fatty acid synthetic enzymes, ACLY and ACC1, and subsequently suppressed cellular lipid accumulation. In conclusion, our study provides critical clues to understand the role of m 6 A and its regulators in ESCA. Moreover, HNRNPA2B1 functions as an oncogenic factor in promoting ESCA progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1, and it may be a promising prognostic biomarker and therapeutic target for human ESCA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

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“…The aberrant expression of methyltransferases and demethylases results in the dysregulation of m 6 A. Methyltransferases are responsible for the erection of m 6 A modification, and m 6 A methylation is removed by demethylases. Of note, m 6 A binding proteins have been shown to recognize target m 6 A-modified RNAs and participate in the biological process and development of human disease ( 33 ).…”

Section: A Methylationmentioning

confidence: 99%

“…The 'reading' of m 6 A methylation marks is achieved through m 6 A RNA binding proteins (RBP), which specifically recognize target m 6 A-modified mRNA and subsequently play a role in the regulation of RNA splicing, fold, transport, translocation, degradation and translation. m 6 A RBPs are involved in the regulation of RNA metabolism and bioprocess ( 33 ). m 6 A-RBPs include YT521-B homology (YTH), heterogenous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) and insulin-like growth factor 2 mRNA-binding protein (IGF2BP) domain ( 39 , 55 , 56 ) ( Fig.…”

Section: A Methylationmentioning

confidence: 99%

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Role of m6A RNA methylation in cardiovascular disease (Review)

et al. 2020

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N 6 -methyladenosine (m 6 A) is the most prevalent and abundant type of internal post-transcriptional RNA modification in eukaryotic cells. Multiple types of RNA, including mRNAs, rRNAs, tRNAs, long non-coding RNAs and microRNAs, are involved in m 6 A methylation. The biological function of m 6 A modification is dynamically and reversibly mediated by methyltransferases (writers), demethylases (erasers) and m 6 A binding proteins (readers). The methyltransferase complex is responsible for the catalyzation of m 6 A modification and is typically made up of methyltransferase-like (METTL)3, METTL14 and Wilms tumor 1-associated protein. Erasers remove methylation by fat mass and obesity-associated protein and ALKB homolog 5. Readers play a role through the recognition of m 6 A-modified targeted RNA. The YT521-B homology domain family, heterogeneous nuclear ribonucleoprotein and insulin-like growth factor 2 mRNA-binding protein serve as m 6 A readers. The m 6 A methylation on transcripts plays a pivotal role in the regulation of downstream molecular events and biological functions, such as RNA splicing, transport, stability and translatability at the post-transcriptional level. The dysregulation of m 6 A modification is associated with cancer, drug resistance, virus replication and the pluripotency of embryonic stem cells. Recently, a number of studies have identified aberrant m 6 A methylation in cardiovascular diseases (CVDs), including cardiac hypertrophy, heart failure, arterial aneurysm, vascular calcification and pulmonary hypertension. The aim of the present review article was to summarize the recent research progress on the role of m 6 A modification in CVD and give a brief perspective on its prospective applications in CVD.

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N⁶‐methyladenosine (m⁶A) RNA modification of G protein‐coupled receptor 133 increases proliferation of lung adenocarcinoma

Zhai

Xie³

et al. 2022

FEBS Open Bio

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significant associated morbidity and mortality rates. However, the mechanism of LUAD tumorigenesis remains far from clear. Here, we scanned downregulated genes involved in LUAD sourced from Cancer Genome Atlas and Gene Expression Omnibus data and focused on G protein-coupled receptor 133 (GPR133). We offer compelling evidence that GPR133 was expressed at low levels in the setting of LUAD and higher expression was positively related with a better prognosis among LUAD patients. Functionally, GPR133 inhibited cell proliferation and tumor growth in vitro and in vivo. Regarding the mechanism, flow cytometry assays and western blot assays showed that GPR133 enhanced p21 and decreased cyclin B1 expression, thus triggered LUAD cells at G2/M-phase arrest. Consistent with this, we evaluated the expression levels of cell-cycle biomarkers and found that Bioinformatics analysis combined with N 6 -methyladenosine (m 6 A; methylation at the N6 position in adenosine) RNA immunoprecipitation-qPCR (MeRIP-qPCR) assay indicated that GPR133 expression was downregulated by this modification. Moreover, we observed that methyltransferase-like 3 was impaired in LUAD and that it is able to significantly increase levels of GPR133 by enhancing its RNA stability. In conclusion, we found that GPR133 expression was downregulated in LUAD via m 6 A modification. Increasing GPR133 levels could suppress LUAD cell proliferation and tumor growth.

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m6A-binding proteins: the emerging crucial performers in epigenetics

Cited by 212 publications

References 120 publications

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Role of m6A RNA methylation in cardiovascular disease (Review)

N⁶‐methyladenosine (m⁶A) RNA modification of G protein‐coupled receptor 133 increases proliferation of lung adenocarcinoma

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m6A-binding proteins: the emerging crucial performers in epigenetics

Cited by 212 publications

References 120 publications

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Role of m6A RNA methylation in cardiovascular disease (Review)

N6‐methyladenosine (m6A) RNA modification of G protein‐coupled receptor 133 increases proliferation of lung adenocarcinoma

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N⁶‐methyladenosine (m⁶A) RNA modification of G protein‐coupled receptor 133 increases proliferation of lung adenocarcinoma