Epigenetic Regulation of m6A Modifications in Human Cancer

Zhao, Wei; Qi, Xiaoqian; Liu, Lina; Ma, Shiqing; Li, Jingwen; Wu, Jie

doi:10.1016/j.omtn.2019.11.022

Cited by 187 publications

(140 citation statements)

References 74 publications

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“…Other methods include MAZTER-seq, RNAmod, FunDMDeep-m 6 A and m 6 A-REF-seq ( 72 - 76 ). Table I summarizes the methods of m 6 A methylation detection ( 7 ). These findings have provided insight into the mammalian genome-wide mapping of m 6 A modifications and unveiled the importance of dynamic mRNA modifications on gene expression.…”

Section: M 6 a Methylationmentioning

confidence: 99%

“…Recent studies have found that, in addition to mRNA, m 6 A also occurs in rRNA, tRNA, small nucleolar RNAs, microRNAs (miRNAs or miRs) and long non-coding RNAs ( 5 , 6 ). The rapid development of next-generation sequencing technology and epigenetic research have assisted in the precise assessment of the in vivo methylation state of m 6 A sites at single-nucleotide resolution ( 7 ). Approximately 1/4 of transcripts harbor m 6 A modifications, which are mainly enriched around the stop codons, within long internal exons in the 5′ and 3′ untranslated regions (UTRs) at the consensus motif RRACH (R=A or G, H=A, C or U) ( 8 ).…”

Section: Introductionmentioning

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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Section: M 6 a Methylationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of m6A RNA methylation in cardiovascular disease (Review)

et al. 2020

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“…N6-methyladenosine (m6A) modification is one of the most frequent chemical modifications in eukaryotic mRNAs. 4 Emerging evidence suggests that aberrant m6A RNA methylation plays a critical role in cancer through various mechanisms, 5,6 such as mRNA stability, splicing, and translation. 7 The level of m6A methylation is regulated by methyltransferases, demethylases, and binding proteins.…”

Section: Introductionmentioning

confidence: 99%

<p>Construction and Validation of an m6A RNA Methylation Regulators-Based Prognostic Signature for Esophageal Cancer</p>

Xu¹,

Pan²,

Pan³

2020

CMAR

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N6-methyladenosine (m6A) is reported to play a critical role in cancer through various mechanisms. We aimed to construct and validate an m6A RNA methylation regulators-based prognostic signature for Esophageal cancer (ESCA). Materials and Methods: The RNA sequencing transcriptome data of 13 m6A RNA methylation regulators as well as clinical data were obtained from The Cancer Genome Atlas (TCGA) ESCA database. The differential expression of the regulators between ESCA tissues and normal tissues was assessed. Consensus clustering was conducted to explore the different ESCA clusters based on the expression of these regulators. LASSO Cox regression analysis was used to generate a prognostic signature based on m6A RNA methylation regulators expression. Results: Eight regulators (KIAA1429, HNRNPC, RBM15, METTL3, WTAP, YTHDF1, YTHDC1, and YTHDF2) were found to be significantly upregulated in ESCA tissues. Significant differences of survival rate and clinicopathological features were found between the two clusters. A prognostic signature, which consists of HNRNPC and ALKBH5, was constructed based on the TCGA ESCA cohort, which can serve as an independent prognostic predictor. The results of bioinformatics analysis were further successfully validated in the clinical ESCA cohort by qRT-PCR and immunohistochemistry staining. Conclusion: Our study constructed and validated an m6A RNA methylation regulatorsbased prognostic signature. This might provide important information for developing diagnostic and therapeutic strategies.

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“…m6A is the most prevalent internal RNA modification. Abnormal changes in m6A levels of regulators are closely related to the development of tumors [21]. Increasing evidence indicates that m6A can regulate gene expression, which in turn regulates the cellular processes of cell self-renewal, differentiation, invasion, and apoptosis [10,22].…”

Section: Discussionmentioning

confidence: 99%

Multiomics profile and prognostic gene signature of m6A regulators in uterine corpus endometrial carcinoma

et al. 2020

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Uterine corpus endometrial carcinoma (UCEC) is the most common type of gynecologic malignancy worldwide. Despite advances in the treatments of UCEC, its incidence and mortality rates are still increasing. N6-methyladenosine (m6A) is the most common form of RNA modification and has attracted increasing interest in cancer pathogenesis and progression. Thus, we aimed to identify the landscape of m6A regulators and build a prognostic gene signature in UCEC. In this study, we first analyzed copy number variations (CNVs), single nucleotide variations (SNVs) and gene expression profiles as well as matched clinical information of UCEC patients from The Cancer Genome Atlas (TCGA) database. Next, we determined that CNVs in m6A regulatory genes had a significant negative impact on patient survival. The mRNA expression levels of a total of 16 m6A regulators were significantly correlated with different CNV patterns. Using univariate Cox regression analysis, IGF2BP1, KIAA1429, IGF2BP3, YTHDF3, and IGF2BP2 were found to be closely associated with UCEC patient survival outcomes. Based on the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression models, we built a 3-gene (IGF2BP3, KIAA1429 and IGF2BP1) signature of m6A regulators with prognostic value in UCEC that could effectively predict patient prognosis (log-rank test p-value < 0.0001). In addition, risk scores were significantly different between patients stratified by tumor stage, SNV, and CNV. Multivariate Cox regression analysis suggested that risk score might be an independent prognostic indicator for the overall survival of patients with UCEC (p-value < 0.05). Gene enrichment analysis indicated that high IGF2BP1 gene expression is associated with cytoplasmic stress granules. KIAA1429 gene expression is associated with cellular nucleic acid metabolism. The expression of the IGF2BP3 gene is associated with RNA binding processes. In conclusion, we determined that genetic alterations in m6A regulatory genes could be effective and reliable biomarkers for UCEC prognosis prediction.

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Epigenetic Regulation of m6A Modifications in Human Cancer

Cited by 187 publications

References 74 publications

Role of m6A RNA methylation in cardiovascular disease (Review)

Role of m6A RNA methylation in cardiovascular disease (Review)

<p>Construction and Validation of an m6A RNA Methylation Regulators-Based Prognostic Signature for Esophageal Cancer</p>

Multiomics profile and prognostic gene signature of m6A regulators in uterine corpus endometrial carcinoma

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