The m6A(m)-independent role of FTO in regulating WNT signaling pathways

Kim, Hyunjoon; Jang, Soohyun; Lee, Young-suk

doi:10.26508/lsa.202101250

Cited by 12 publications

(4 citation statements)

References 64 publications

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“…Given the growing evidences that m6A is associated with Wnt signaling 5 , 6 , while recognizing that Wnt/β-catenin plays an inevitable role in GBM 7 – 9 , there may be possible mechanisms for their yet to be elucidated interplay in the pathogenesis of GBM. Concerning the functional regulation of m6A, the fine-tuning and interactions between the m6A and long non-coding RNAs (lncRNA) axis have been considered.…”

Section: Introductionmentioning

confidence: 99%

Systematic integration of m6A regulators and autophagy-related genes in combination with long non-coding RNAs predicts survival in glioblastoma multiforme

Sharma,

Wang,

et al. 2023

Sci Rep

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Glioblastoma multiforme (GBM) is probably the only tumor in which a unique epigenetic alteration, namely methylation of the MGMT gene, possesses direct clinical relevance. Now with the emergence of aberrant N6 methyladenosine (m6A) modifications (the most common epigenetic modification of mRNA, closely linked to the autophagy process) in cancer, the epi-transcriptomic landscape of GBM pathobiology has been expanded. Considering this, herein, we systematically analyzed m6A regulators, assessed their correlation with autophagy-related genes (ATG), and established a long non-coding RNAs (lncRNA)-dependent prognostic signature (m6A-autophagy-lncRNAs) for GBM. Our analysis identified a novel signature of five long non-coding RNAs (lncRNAs: ITGA6-AS1, AC124248.1, NFYC-AS1, AC025171.1, and AC005229.3) associated with survival of GBM patients, and four among them clearly showed cancer-associated potential. We further validated and confirmed the altered expression of two lncRNAs (AC124248.1, AC005229.3) in GBM associated clinical samples using RT-PCR. Concerning the prognostic ability, the obtained signature determined high-/low-risk groups in GBM patients and showed sensitivity to anticancer drugs. Collectively, the m6A-autophagy-lncRNAs signature presented in the study is clinically relevant and is the first attempt to systematically predict the potential interaction between the three key determinants (m6A, autophagy, lncRNA) in cancer, particularly in GBM.

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Section: Introductionmentioning

confidence: 99%

Systematic integration of m6A regulators and autophagy-related genes in combination with long non-coding RNAs predicts survival in glioblastoma multiforme

Sharma,

Wang,

et al. 2023

Sci Rep

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“…WTAP has been reported to be associated with a number of signaling pathways, such as TGFβ (Li et al, 2020b), hippo (Hu et al, 2020), NF-κB , and Hedgehog pathways (Wei et al, 2022). FTO is associated with various signaling pathways, for example, PKA/CREB (Hu et al, 2022), TNF-α (Li et al, 2022b), ERK (Xiao et al, 2022b), WNT (Kim et al, 2022) and JAK2/ STAT3 pathways (Shen et al, 2021). ALKBH5 is involved in many signaling pathways, including WNT (Lin et al, 2022), PTEN/AKT (He et al, 2021), NF-κB (Qu et al, 2022), AKT (Wang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of differences in N6-methyladenosine RNA methylomes in Helicobacter pylori infection

Lin

Cheng

et al. 2023

Front. Cell Dev. Biol.

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Background:Helicobacter pylori (H.pylori) infection is an important factor in the occurrence of human gastric diseases, but its pathogenic mechanism is not clear. N6-methyladenosine (m6A) is the most prevalent reversible methylation modification in mammalian RNA and it plays a crucial role in controlling many biological processes. However, there are no studies reported that whether H. pylori infection impacts the m6A methylation of stomach. In this study, we measured the overall level changes of m6A methylation of RNA under H. pylori infection through in vitro and in vivo experiment.Methods: The total quantity of m6A was quantified in gastric tissues of clinical patients and C57 mice with H. pylori infection, as well as acute infection model [H. pylori and GES-1 cells were cocultured for 48 h at a multiplicity of infection (MOI) from of 10:1 to 50:1]. Furthermore, we performed m6A methylation sequencing and RNA-sequencing on the cell model and RNA-sequencing on animal model.Results: Quantitative detection of RNA methylation showed that H. pylori infection group had higher m6A modification level. M6A methylation sequencing identified 2,107 significantly changed m6A methylation peaks, including 1,565 upregulated peaks and 542 downregulated peaks. A total of 2,487 mRNA was upregulated and 1,029 mRNA was downregulated. According to the comprehensive analysis of MeRIP-seq and RNA-seq, we identified 200 hypermethylation and upregulation, 129 hypermethylation but downregulation, 19 hypomethylation and downregulation and 106 hypomethylation but upregulation genes. The GO and KEGG pathway analysis of these differential methylation and regulatory genes revealed a wide range of biological functions. Moreover, combining with mice RNA-seq results, qRT- PCR showed that m6A regulators, METTL3, WTAP, FTO and ALKBH5, has significant difference; Two key genes, PTPN14 and ADAMTS1, had significant difference by qRT- PCR.Conclusion: These findings provide a basis for further investigation of the role of m6A methylation modification in H. pylori-associated gastritis.

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“…m6A methylation modification plays an important role in maintaining stem cell metabolism [ 29 ], immune homeostasis [ 30 ], tumor immune microenvironment [ 31 ], immune suppression and escape [ 32 ], and other biological regulations. m6A methylation modification can also affect cell differentiation and proliferation by affecting the expression of transcription factors [ 33 , 34 ]. m6A methylation is modified by altering RNA folding and structure, which enhances mRNA export and translation [ 10 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis and Functional Characteristics of Differential Expression of N6-Methyladenosine Methylation Modification in the Whole Transcriptome of Rheumatoid Arthritis

Wan

Liu

Huang

et al. 2022

Mediators of Inflammation

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N6-methyladenosine (m6A) modification is the most prevalent chemical modification in eukaryotic mRNA and is associated with the development of various immune diseases. However, the role of m6A methylation in rheumatoid arthritis (RA) development is unclear. We preliminarily explored the role of m6A methylation-related mRNAs in RA for its clinical application. The discovery of m6A methylation-modifying genes in this study may provide a fresh perspective on the development of drugs for RA treatment. High-throughput sequencing combined with methylated RNA immunoprecipitation (MeRIP-seq) and RNA sequencing were used to assess whole-transcriptome m6A modifications in the synovium of patients with RA. The relationship between m6A-modified target genes and RA inflammation and macrophages was determined. The expression of the m6A-modified significant transcript-enriched inflammatory signaling pathway was assessed through animal experiments. Differentially expressed m6A genes were correlated with macrophage activation involved in immune response, vascular endothelium, MAPK signaling pathway, PI3K − Akt signaling pathway, and other inflammatory processes. Furthermore, combined analysis with m6A-seq and RNA-seq revealed 120 genes with significant changes in both m6A modification and mRNA expression. We selected the top 3 candidate mRNAs that were upregulated and downregulated simultaneously. The expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) mRNA and protein in RA patients was lower than that in healthy control (HC). SHC-binding protein 1 (SHCBP1) and neurexophilin-3 (NXPH3) mRNA expressions were increased in RA patients. The expression of M1 macrophages was increased in RA patients. RA markers are such as rheumatoid factor (RF) and peptide containing citrulline (CCP). Further animal experiments showed that the expression of synovial MAPK, PI3K, and Akt1 proteins in the RA model was increased, and the PTEN, p-PTEN protein expression was decreased. PI3K, Akt1, PTEN, and p-PTEN were correlated to RA joint inflammation. This study revealed a unique pattern of differential m6A methylation modifications in RA and concluded that m6A modification is related to the occurrence of RA synovial inflammation.

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The m6A(m)-independent role of FTO in regulating WNT signaling pathways

Cited by 12 publications

References 64 publications

Systematic integration of m6A regulators and autophagy-related genes in combination with long non-coding RNAs predicts survival in glioblastoma multiforme

Systematic integration of m6A regulators and autophagy-related genes in combination with long non-coding RNAs predicts survival in glioblastoma multiforme

Comprehensive analysis of differences in N6-methyladenosine RNA methylomes in Helicobacter pylori infection

Comprehensive Analysis and Functional Characteristics of Differential Expression of N6-Methyladenosine Methylation Modification in the Whole Transcriptome of Rheumatoid Arthritis

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