Cross-Talk between N6-Methyladenosine and Their Related RNAs Defined a Signature and Confirmed m6A Regulators for Diagnosis of Endometriosis

Xiaotong Wang, Xibo Zhao, Jing Wang, Han Wu, Yan Cheng, Qiuyan Guo, Tian Liang, Guangmei Zhang
International journal of molecular sciences · 2023 · vol. 24(2) , pp. 1665 · doi:10.3390/ijms24021665 · PMID:36675186 · W4316371987
article OA: gold CC0 ⤵ 7 in-corpus citations
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This study identified METTL3 and YTHDF2 as diagnostic targets for endometriosis by analyzing m6A modification patterns and their correlation with immune microenvironment and clinical features.

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Abstract

An RNA modification known as N6-methyladenosine (m6A) interacts with a range of coding and non-coding RNAs. The majority of the research has focused on identifying m6A regulators that are differentially expressed in endometriosis, but it has ignored their mechanisms that are derived from the alterations of modifications among RNAs, affecting the disease progression primarily. Here, we aimed to investigate the potential roles of m6A regulators in the diagnostic potency, immune microenvironment, and clinicopathological features of endometriosis through interacting genes. A GEO cohort was incorporated into this study. Variance expression profiling was executed via the "limma" R package. Pearson analysis was performed to investigate the correlations among 767 interacting lncRNAs, 374 interacting mRNAs, and 23 m6A regulators. K-means clustering analysis, based on patterns of mRNA modifications, was applied to perform clinical feature analysis. Infiltrating immune cells and stromal cells were calculated using the Cibersort method. An m6A-related risk model was created and supported by an independent risk assay. LASSO regression analysis and Cox analyses were implemented to determine the diagnostic genes. The diagnostic targets of endometriosis were verified using PCR and the WB method. Results: A thorough investigation of the m6A modification patterns in the GEO database was carried out, based on mRNAs and lncRNAs related to these m6A regulators. Two molecular subtypes were identified using unsupervised clustering analysis, resulting in further complex infiltration levels of immune microenvironment cells in diversified endometriosis pathology types. We identified two m6A regulators, namely METTL3 and YTHDF2, as diagnostic targets of endometriosis following the usage of overlapping genes to construct a diagnostic m6A signature of endometriosis through multivariate logistic regression, and we validated it using independent GSE86534 and GSE105764 cohorts. Finally, we found that m6A alterations might be one of the important reasons for the progression of endometriosis, especially with significant downregulation of the expressions of METTL3 and YTHDF2. Finally, m6A modification patterns have significant effects on the diversity and complexity of the progression and immune microenvironment, and might be key diagnostic markers for endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Methyltransferases Methyltransferases Methyltransferases Methyltransferases Methyltransferases

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