ABSTRACT Reperfusion therapy after acute myocardial infarction can induce myocardial ischemia-reperfusion injury (IRI). Novel evidence has illustrated that N6-methyladenosine (m6A) modification modulates the myocardial IRI progression. Here, our study focuses on the role of m6A methyltransferase fat mass and obesity-associated protein (FTO) in myocardial ischemia/reoxygenation injury and explores potential regulatory mechanisms. Results discovered that FTO down-expressed in myocardial IRI mice and hypoxia/reoxygenation (H/R)-induced cardiomyocytes. Functionally, FTO overexpression attenuated the H/R-induced apoptosis and inflammation of cardiomyocytes. Mechanistically, methylated RNA immunoprecipitation quantitative polymerase chain reaction (MeRIP-qPCR) assay and RIP assay revealed that Yap1 mRNA acted as the target of FTO in cardiomyocytes. Moreover, FTO uninstalled the methylation of Yap1 mRNA, and enforced the stability of Yap1 mRNA. Taken together, our study reveals the role of FTO in H/R-induced myocardial cell injury via m6A-dependent manner, which may provide a new approach to improve myocardial IRI.

https://www.tandfonline.com/doi/pdf/10.1080/21655979.2022.2030572?needAccess=true

m6A demethylase FTO regulates the apoptosis and inflammation of cardiomyocytes via YAP1 in ischemia-reperfusion injury

Musculoskeletal disorder (MSD) are a class of inflammatory and degener‐ative diseases, but the precise molecular mechanisms are still poorly understood. Noncoding RNA (ncRNA) N6‐methyladenosine (m6A) modification plays an essential role in the pathophysiological process of MSD. This review summarized the interaction between m6A RNA methylation and ncRNAs in the molecular regulatory mechanism of MSD. It provides a new perspective for the pathophysiological mechanism and ncRNA m6A targeted therapy of MSD.

Novel insights into the interaction between N6‐methyladenosine methylation and noncoding RNAs in musculoskeletal disorders

m6A modification of circSPECC1 suppresses RPE oxidative damage and maintains retinal homeostasis.

Background Glioblastoma multiforme (GBM), the most prevalent and aggressive of primary malignant central nervous system tumors (grade IV), has a poor clinical prognosis. This study aimed to assess and predict the survival of GBM patients by establishing an m6A-related lncRNA signaling model and to validate its validity, accuracy and applicability. Methods RNA sequencing data and clinical data of GBM patients were obtained from TCGA data. First, m6A-associated lncRNAs were screened and lncRNAs associated with overall survival in GBM patients were obtained. Subsequently, the signal model was established using LASSO regression analysis, and its accuracy and validity are further verified. Finally, GO enrichment analysis was performed, and the influence of this signature on the immune regulation response and anticancer drug sensitivity of GBM patients was discussed. Results The signature constructed by four lncRNAs AC005229.3, SOX21-AS1, AL133523.1, and AC004847.1 is obtained. Furthermore, the signature proved to be effective and accurate in predicting and assessing the survival of GBM patients and could function independently of other clinical characteristics (Age, Gender and IDH1 mutation). Finally, Immunosuppression-related factors, including APC co-inhibition, T-cell co-inhibition, CCR and Check-point, were found to be significantly up-regulated in GBM patients in the high-risk group. Some chemotherapeutic drugs (Doxorubicin and Methotrexate) and targeted drugs (AZD8055, BI.2536, GW843682X and Vorinostat) were shown to have higher IC50 values in patients in the high-risk group. Conclusion We constructed an m6A-associated lncRNA risk model to predict the prognosis of GBM patients and provide new ideas for the treatment of GBM. Further biological experiments can be conducted on this basis to validate the clinical value of the model. 

/pdf/construction-of-m6a-related-lncrna-prognostic-signature-1e950t6s.pdf

Construction of m6A-Related lncRNA Prognostic Signature Model and Immunomodulatory Effect in Glioblastoma Multiforme

Cardiac ischemia/reperfusion (I/R) injury is a complicated pathological event, which has close association with pyroptosis. This study uncovered the regulatory mechanisms of fat mass and obesity-associated protein (FTO) in NLRP3-mediated pyroptosis during cardiac I/R injury. H9c2 cells were stimulated with oxygen–glucose deprivation/reoxygenation (OGD/R). Cell viability and pyroptosis were detected by CCK-8 and flow cytometry. Western blotting or RT-qPCR was performed to analyze target molecule expression. NLRP3 and Caspase-1 expression was observed by immunofluorescence staining. IL-18 and IL-1β production was detected by ELISA. The total m6A and m6A level of CBL was determined by dot blot assay and methylated RNA immunoprecipitation-qPCR, respectively. The interaction between IGF2BP3 and CBL mRNA was confirmed by RNA pull-down and RIP assays. The protein interaction between CBL and β-catenin and β-catenin ubiquitination were evaluated by Co-IP. Myocardial I/R model was established in rats. We determined infarct size by TTC staining and pathological changes by H&E staining. LDH, CK-MB, LVFS, and LVEF were also assessed. FTO and β-catenin were down-regulated, while CBL was up-regulated by OGD/R stimulation. FTO/β-catenin overexpression or CBL silencing restrained OGD/R-induced NLRP3 inflammasome-mediated pyroptosis. CBL repressed β-catenin expression via ubiquitination and degradation. FTO reduced the mRNA stability of CBL by inhibiting m6A modification. CBL-mediated ubiquitination and degradation of β-catenin were involved in FTO-induced pyroptosis inhibition during myocardial I/R injury. FTO inhibits NLRP3-mediated pyroptosis to attenuate myocardial I/R injury via repressing CBL-induced ubiquitination degradation of β-catenin. 

<scp>FTO</scp> represses <scp>NLRP3</scp> ‐mediated pyroptosis and alleviates myocardial ischemia–reperfusion injury via inhibiting <scp>CBL</scp> ‐mediated ubiquitination and degradation of β‐catenin

The exploration of dynamic N6-methyladenosine (m6A) RNA modification in mammalian cells has attracted great interest in recent years. M6A modification plays pivotal roles in multiple biological and pathological processes, including cellular reprogramming, fertility, senescence, and tumorigenesis. In comparison with growing research unraveling the effects of m6A modifications on eukaryotic messenger RNAs, reports of the association between noncoding RNAs and m6A modification are relatively limited. Noncoding RNAs that undergo m6A modification are capable of regulating gene expression and also play an important role in epigenetic regulation. Moreover, the homeostasis of m6A modification can be affected by noncoding RNAs across a broad spectrum of biological activities. Importantly, fine-tuning and interaction between these processes are responsible for cell development, as well as the initiation and progression of the disease. Hence, in this review, we provide an account of recent developments, revealing biological interactions between noncoding RNAs and m6A modification, and discuss the potential clinical applications of interfering with m6A modification.

/pdf/n6-methyladenosine-sculpted-regulatory-landscape-of-34duh0k22m.pdf

N6-Methyladenosine-Sculpted Regulatory Landscape of Noncoding RNA.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Hao Wang

Author Tools

Chat about Author

Papers

N6-Methyladenosine-Sculpted Regulatory Landscape of Noncoding RNA.