Exploring the potential mechanisms of m6A modification in septic acute respiratory distress syndrome: a bioinformatics analysis

TL;DR

This study explores how m6A modification, specifically through the WTAP gene, contributes to the development of ARDS in sepsis patients.

Contribution

The study identifies WTAP as a key m6A regulator in ARDS and links it to immune cell infiltration and disease progression.

Findings

WTAP, HNRNPA2B1, and HNRNPC show extensive expression in the ARDS microenvironment.

WTAP variation correlates with distinct sepsis subgroups and is associated with the brown gene module.

WTAP promotes ARDS progression by enhancing m6A methylation and immune cell infiltration.

Abstract

Acute respiratory distress syndrome (ARDS) remains a leading cause of mortality in intensive care units. The N6-methyladenosine (m6A) mRNA modification is critical in various pathological conditions, yet its role in the ARDS microenvironment, particularly at the single-cell level, remains poorly understood.

Single-cell and bulk RNA-sequencing datasets were sourced from the GEO databases. Bioinformatics and experimental approaches were employed to investigate the associations between m6A regulators and hub genes in ARDS.

WTAP, HNRNPA2B1, and HNRNPC exhibited extensive expression within the ARDS microenvironment. Consensus clustering analysis segregated patients with sepsis into distinct subgroups, with WTAP showing significant variation across these groups. Weighted gene co-expression network analysis (WGCNA) identified the brown module as most associated with WTAP, revealing five hub genes. Validation experiments confirmed high expression levels of WTAP and MYC in lung tissues. Functional assays further demonstrated that WTAP enhances ARDS progression.

In conclusion, bioinformatics analysis and preliminary experimental data suggest that WTAP promotes ARDS onset and progression by regulating m6A methylation and facilitating immune cell infiltration.

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