Editing regulatory network in non-small cell lung cancer: implications for immunity and metastasis

RNA editing plays critical roles in cancer development, and multiple editing events collectively exert greater effects than individual events. However, the coordinated impact of RNA editing remains poorly understood.

A comprehensive framework was proposed to investigate interactions among RNA editing events, capturing both the global editing landscape and site-specific functional effects. The resulting RNA editing modules were further explored to reveal gene interactions and regulatory mechanisms from the perspective of RNA editing.

Using non-small cell lung cancer as an example, we identified more than 12 modules involved in immune regulation and metastasis-related processes, demonstrating their clinical relevance. Mechanistically, RNA editing influenced miRNA-mediated regulation of EIF2AK2 and PRKAR2A, transcription factor activity of AHR, and RNA-binding regulation of DDX3X, highlighting its role in shaping gene regulatory networks.

Collectively, this study provides a systematic, module-based framework for understanding coordinated RNA editing, offering new insights into RNA editing–mediated gene interactions and revealing a complementary approach to study molecular mechanisms of diseases.