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

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.

The Effect of Rubus idaeus Polyphenols Extract in Induced Endometriosis in Rats

“…Thus, catechins possess anti-inflammatory activities by regulating the activation/deactivation of different inflammatory and oxidative stress cell signaling pathways like nuclear factor-kappa B (NF-κB), transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), mitogen-activated protein kinases (MAPKs) or signal transducer, and the activator of transcription 1/3 (STAT1/3) pathways [ 77 ]. Also, according to the literature, another possible effect of phenolics has been reported on epi transcriptomic pathways, such as the fact that m6A modification might modulate TGFβ signaling [ 78 , 79 ] as a result of its activation during the epithelial to mesenchymal transition process characteristic of endometriosis [ 80 , 81 ].…”

Promotion of BST2 expression by the transcription factor IRF6 affects the progression of endometriosis

“…The immune system is thought to play a major role in the survival of these tissues and cells in the pelvic microenvironment by causing immune tolerance, suppressing immunosurveillance, and preventing their phagocytosis by immune cells ( 8 ). Based on multiple lines of evidence, women with endometriosis not only exhibit an altered immune status in the endometrium but also exhibit altered peripheral immune responses ( 7 , 9 ). The aberrant changes that occur in the peritoneal environment also result in the recruitment of a large number of immune cells, inflammatory-associated proteins, and relevant cytokines, and these factors are all found to be related to the pathophysiology of endometriosis ( 8 , 10 ).…”