Profiling the m6A-regulated RNA expression patterns and alternative splicing features in esophageal carcinoma

Kong, Lingyun; Gao, Fei; Fang, Zhao; Ran, Xia; Cai, Cifeng; Wang, Weixin; Huang, Dabing; Li, Zhenyu; Yi, Qiyi; Zang, Chunbao; Pu, Youguang

doi:10.1016/j.gendis.2022.12.009

Cited by 2 publications

(4 citation statements)

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“…Our research showed that the independent expression of FTO was not significantly correlated with the prognosis of esophageal cancer patients, which is different from the mechanism of ALKBH5 (Fig. S1 A, B) (Kong et al 2023 ). Analysis of esophageal cancer patients with higher FTO/METTL14 ratios revealed poorer prognoses than patients with lower FTO/METTL14 ratios (Fig.…”

Section: Resultscontrasting

confidence: 69%

“…Currently, only two proteins have been found to have demethylase activity via m 6 A modification. On the basis of our previous finding that ALKBH5 expression is positively correlated with the prognosis of esophageal cancer patients, while for the other m 6 A demethylase protein FTO, we found that it can promote the proliferation and invasion of esophageal cancer cells but is not related to the prognosis of esophageal cancer patients (Kong et al 2023 ). Based on these results, we investigated the correlation between the combined effect of FTO and multiple m 6 A regulatory proteins and the prognosis of esophageal cancer patients and found that an increase in the FTO/METTL14 ratio can lead to poor prognosis.…”

Section: Discussionmentioning

confidence: 71%

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The antagonistic effect of FTO on METTL14 promotes AKT3 m6A demethylation and the progression of esophageal cancer

Wei,

Zhao,

Kong

et al. 2024

J Cancer Res Clin Oncol

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Background As the most abundant modification in eukaryotic messenger RNAs (mRNAs), N6-methyladenosine (m6A) plays vital roles in many biological processes. Methods Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen for m6A targets in esophageal cancer cells and patients. The role of m6A RNA methylase in esophageal cancer was also analyzed using bioinformatics. In vitro and in vivo experiments were used to analyze gene expression and function. CCK-8, colony formation, cell apoptosis and immunofluorescence staining assays were performed to evaluate the proliferation, migration and invasion of esophageal cancer cells, respectively. Western blot analysis, RNA stability, RIP and luciferase reporter assays were performed to elucidate the underlying mechanism involved. Results We found that the m6A demethylase FTO was significantly upregulated in esophageal cancer cell lines and patient tissues. In vivo and in vitro assays demonstrated that FTO was involved in the proliferation and apoptosis of esophageal cancer cells. Moreover, we found that the m6A methyltransferase METTL14 negatively regulates FTO function in esophageal cancer progression. FTO alone is not related to the prognosis of esophageal cancer, and its function is antagonized by METTL14. By using transcriptome-wide m6A-seq and RNA-seq assays, we revealed that AKT3 is a downstream target of FTO and acts in concert to regulate the tumorigenesis and metastasis of esophageal cancer. Taken together, these findings provide insight into m6A-mediated tumorigenesis in esophageal cancer and could lead to the design of new therapeutic strategies.

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Section: Resultscontrasting

confidence: 69%

Section: Discussionmentioning

confidence: 71%

The antagonistic effect of FTO on METTL14 promotes AKT3 m6A demethylation and the progression of esophageal cancer

Wei,

Zhao,

Kong

et al. 2024

J Cancer Res Clin Oncol

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“…Furthermore, m6A‐related alternative splicing plays a role in glioma progression through its influence on the immune‐microenvironment, making it a potential biomarker for prognostic assessment and personalised treatment strategies in patients with glioma 142,143 . Similarly, in oesophageal carcinoma, a negative correlation between m6A patterns and alternative splicing features in individual patients has been observed 144 . Likewise, the involvement of m6A‐dependent alternative splicing and its regulatory players in clinical features suggests their potential as prognostic biomarkers for patients with non‐small cell lung cancer 145 .…”

Section: Clinical Implications Of M6a Methylation In Alternative Spli...mentioning

confidence: 99%

“… 142 , 143 Similarly, in oesophageal carcinoma, a negative correlation between m6A patterns and alternative splicing features in individual patients has been observed. 144 Likewise, the involvement of m6A‐dependent alternative splicing and its regulatory players in clinical features suggests their potential as prognostic biomarkers for patients with non‐small cell lung cancer. 145 These findings underscore the clinical relevance of alternative splicing in the context of m6A modification, and the alternative splicing of the m6A methylation machinery may represent an uncharted pathway in mediating tumour progression.…”

Section: Clinical Implications Of M6a Methylation In Alternative Spli...mentioning

confidence: 99%

Crosstalk between m6A modification and alternative splicing during cancer progression

Zhu,

Huo,

Zhang

et al. 2023

Clinical & Translational Med

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BackgroundN6‐methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is added by m6A methyltransferases, removed by m6A demethylases and recognised by m6A‐binding proteins. This modification significantly influences carious facets of RNA metabolism and plays a pivotal role in cellular and physiological processes.Main bodyPre‐mRNA alternative splicing, a process that generates multiple splice isoforms from multi‐exon genes, contributes significantly to the protein diversity in mammals. Moreover, the presence of crosstalk between m6A modification and alternative splicing, with m6A modifications on pre‐mRNAs exerting regulatory control, has been established. The m6A modification modulates alternative splicing patterns by recruiting specific RNA‐binding proteins (RBPs) that regulate alternative splicing or by directly influencing the interaction between RBPs and their target RNAs. Conversely, alternative splicing can impact the deposition or recognition of m6A modification on mRNAs. The integration of m6A modifications has expanded the scope of therapeutic strategies for cancer treatment, while alternative splicing offers novel insights into the mechanistic role of m6A methylation in cancer initiation and progression.ConclusionThis review aims to highlight the biological functions of alternative splicing of m6A modification machinery and its implications in tumourigenesis. Furthermore, we discuss the clinical relevance of understanding m6A‐dependent alternative splicing in tumour therapies.

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Profiling the m6A-regulated RNA expression patterns and alternative splicing features in esophageal carcinoma

Cited by 2 publications

References 5 publications

The antagonistic effect of FTO on METTL14 promotes AKT3 m6A demethylation and the progression of esophageal cancer

The antagonistic effect of FTO on METTL14 promotes AKT3 m6A demethylation and the progression of esophageal cancer

Crosstalk between m6A modification and alternative splicing during cancer progression

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