The context-dependent duality of MEG3: a pivotal regulator and promising target in inflammation-associated diseases

Chronic inflammation, governed by epigenetic networks, underlies a broad spectrum of diseases. In this context, the long non-coding RNA maternally expressed gene 3 (MEG3) has emerged as a pivotal molecular node. This review consolidates current knowledge on MEG3, detailing its genetics, expression regulation, and core mechanisms-primarily its role as a competing endogenous RNA (posttranscriptional regulation) and as a scaffold for chromatin modifiers to modulate inflammatory pathways.

The defining feature of MEG3 is the pronounced context-dependent duality, acting as either a protective factor or a pathogenic driver. Herein, we systematically catalog its dysregulation patterns and implications across arthritic, metabolic, respiratory, digestive, renal, cardiovascular, and cerebrovascular diseases. Furthermore, MEG3 consistently correlates with disease activity, underscoring its biomarker potential, and preclinical evidence supports MEG3 as a therapeutic target.

Clinical translation is currently hindered by inconsistent findings arising from cellular heterogeneity and unstratified disease stages, as well as a lack of tissue-specific delivery strategies. Future research should leverage high-resolution transcriptomics technologies to dissect its precise cell-type-specific functions and enable patient stratification, while integrating molecular diagnostics, interdisciplinary collaboration, and drug design. Such efforts will be essential to harness MEG3 for developing novel diagnostic and therapeutic strategies against inflammation-associated diseases.