RNA modifications in brain tumorigenesis

Huang, Albert; Delaidelli, Alberto; Sorensen, Poul H.

doi:10.1186/s40478-020-00941-6

Cited by 16 publications

(14 citation statements)

References 147 publications

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“…RNA m 6 A modification is an emerging field in the study of tumorigenicity and therapy resistance of glioma [ 7 , 11 , 27 , 32 ]. Our previous study also showed that the expression pattern of m 6 A ‘writers,’ ‘erasers,’ and ‘readers’ are highly associated with malignant progression and prognosis of glioma in both CGGA and TCGA cohorts [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent advances in understanding RNA N 6,2′- O -dimethyladenosine (m 6 A) modification have provided new insights into the molecular mechanism of malignant progression of diffuse gliomas [ 7 – 9 ]. Similar to DNA and protein modification, m 6 A is dynamically regulated by methyltransferases (‘writers’) and demethylases (‘erasers’) [ 10 , 11 ]. m 6 A can influence the entire RNA life cycle, including alternative polyadenylation, pre-RNA processing, RNA export from the nucleus to the cytoplasm, RNA translation, and RNA decay, through binding with different ‘readers’ of m 6 A [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

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YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m6A modification to activate NF-κB and promote the malignant progression of glioma

et al. 2021

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Background The prognosis for diffuse gliomas is very poor and the mechanism underlying their malignant progression remains unclear. Here, we aimed to elucidate the role and mechanism of the RNA N6,2′-O-dimethyladenosine (m6A) reader, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), in regulating the malignant progression of gliomas. Methods YTHDF2 mRNA levels and functions were assessed using several independent datasets. Western blotting, quantitative polymerase chain reaction, and immunohistochemistry were used to evaluate the expression levels of YTHDF2 and other molecules in human and mouse tumor tissues and cells. Knockdown and overexpression were used to evaluate the effects of YTHDF2, methyltransferase-like 3 (METTL3), and UBX domain protein 1 (UBXN1) on glioma malignancy in cell and orthotopic xenograft models. RNA immunoprecipitation (RIP), methylated RIP, and RNA stability experiments were performed to study the mechanisms underlying the oncogenic role of YTHDF2. Results YTHDF2 expression was positively associated with a higher malignant grade and molecular subtype of glioma and poorer prognosis. YTHDF2 promoted the malignant progression of gliomas in both in vitro and in vivo models. Mechanistically, YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-κB activation. We further revealed that UBXN1 overexpression attenuated the oncogenic effect of YTHDF2 overexpression and was associated with better survival in patients with elevated YTHDF2 expression. Conclusions Our findings confirmed that YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-κB activation via UBXN1 with a primary focus on m6A modification.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m6A modification to activate NF-κB and promote the malignant progression of glioma

et al. 2021

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“…Serving as an epitranscriptomic layer of gene regulation, dynamic m 6 A modification has been demonstrated to play vital roles in a wide range of RNA metabolic processes ( Roignant and Soller, 2017 ; Yang et al , 2018 ; Shen et al , 2019 ; Huang et al , 2020 ). We found that although the global abundance and configuration of m 6 A were comparable between hybrid and parents, the number of genes harboring m 6 A sites was increased in the hybrid ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-wide analysis of epitranscriptome and translational efficiency associated with heterosis in maize

Luo

Wang

Jia

et al. 2021

Journal of Experimental Botany

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Heterosis has been extensively utilized to increase productivity in crop, yet underlying molecular mechanisms remain largely elusive. Here, we generated transcriptome-wide profiles of mRNA abundance, m 6A methylation, and translational efficiency from the maize F1 hybrid B73×Mo17 and its two parental lines to ascertain contributions of each regulatory layer to heterosis at the seedling stage.We documented that although the global abundance and distribution configuration of m 6A maintained unchanged, a greater number of genes have gained m 6A modification in hybrid. m 6A modification and translational efficiency exhibited superior variations between hybrid and parents as compared with mRNA abundance. In hybrid, the vast majority of genes with m 6A modification exhibited non-additive expression pattern, the percentage of which was exceedingly higher than that of differential genes at mRNA abundance and translational efficiency. Non-additive genes involved in different biological processes were hierarchically coordinated by discrete combinations of three regulatory layers. These findings suggest that transcriptional and post-transcriptional regulations on gene expression adopt divergent approaches to participate in the formation of heterosis in hybrid. Overall, the integrated multi-omics analysis provides a valuable portfolio for interpreting transcriptional and post-transcriptional regulation on gene expression in maize hybrid, and paves new avenues for exploring molecular mechanisms underlying hybrid vigor.

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“…Reversible RNA modifications, including N1-Methyladenosine (m 1 A), 5-Methylcytosine (m 5 C), and N6-Methyladenosine (m 6 A), have garnered substantial attention from oncologists in recent years [ 6 ]. Among these modifications, m 6 A is recognized as the most prevalent internal modification of poly-adenylated mRNAs and long non-coding RNAs in eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of the transcriptome‐wide m6A methylome in invasive malignant pleomorphic adenoma

et al. 2021

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Background Invasive malignant pleomorphic adenoma (IMPA) is a highly invasive parotid gland tumor and lacks effective therapy. N6-Methyladenosine (m6A) is the most prevalent post-transcriptional modification of mRNAs in eukaryotes and plays an important role in the pathogenesis of multiple tumors. However, the significance of m6A-modified mRNAs in IMPA has not been elucidated to date. Hence, in this study, we attempted to profile the effect of IMPA in terms of m6A methylation in mRNA. Methods Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were utilized to acquire the first transcriptome-wide profiling of the m6A methylome map in IMPA followed by bioinformatics analysis. Results In this study, we obtained m6A methylation maps of IMPA samples and normal adjacent tissues through MeRIP-seq. In total, 25,490 m6A peaks associated with 13,735 genes were detected in the IMPA group, whereas 33,930 m6A peaks associated with 18,063 genes were detected in the control group. Peaks were primarily enriched within coding regions and near stop codons with AAACC and GGAC motifs. Moreover, functional enrichment analysis demonstrated that m6A-containing genes were significantly enriched in cancer and metabolism relevant pathways. Furthermore, we identified a relationship between the m6A methylome and the RNA transcriptome, indicating a mechanism by which m6A modulates gene expression. Conclusions Our study is the first to provide comprehensive and transcriptome-wide profiles to determine the potential roles played by m6A methylation in IMPA. These results may open new avenues for in-depth research elucidating the m6A topology of IMPA and the molecular mechanisms governing the formation and progression of IMPA.

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RNA modifications in brain tumorigenesis

Cited by 16 publications

References 147 publications

YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m6A modification to activate NF-κB and promote the malignant progression of glioma

YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m6A modification to activate NF-κB and promote the malignant progression of glioma

Transcriptome-wide analysis of epitranscriptome and translational efficiency associated with heterosis in maize

Comprehensive analysis of the transcriptome‐wide m6A methylome in invasive malignant pleomorphic adenoma

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