Epigenetic crosstalk between miR-144 and DNMT3A in the pathogenesis of chronic obstructive pulmonary disease: a narrative review

This review consolidates and evaluates current evidence on the epigenetic interaction between microRNA-144 [miR-144] and DNA methyltransferase 3A (DNMT3A) and its collective role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The available literature was narratively synthesized to provide a comprehensive overview of the current evidence regarding the mechanistic, epigenetic, and clinical implications of miR-144 and DNMT3A in COPD. Across the included studies, miR-144 was consistently reported to be upregulated in smokers and individuals with COPD, with parallel findings demonstrating a reduction in DNMT3A expression and associated hypomethylation of key inflammatory gene promoters. Functional assays and mechanistic analyses further substantiated that miR-144 directly targets and suppresses DNMT3A, leading to impaired methyltransferase activity, dysregulated DNA methylation patterns, heightened oxidative stress, and enhanced secretion of pro-inflammatory cytokines. These molecular alterations collectively contribute to a self-sustaining cycle of chronic inflammation, epithelial injury, and airway remodeling, which are potential features of COPD progression. The literature that is now available indicates that DNMT3A-mediated epigenetic regulation and miR-144 dysregulation both contribute to important molecular processes implicated in the pathophysiology of COPD, such as oxidative stress, inflammation, and aberrant gene regulation. There is currently little direct mechanistic evidence connecting the miR-144–DNMT3A axis in COPD, despite the literature supporting the individual roles of these molecules. Therefore, rather than being a completely developed pathway, this regulatory interaction should be viewed as an evolving mechanistic framework. To fully understand its diagnostic, prognostic, and therapeutic potential in COPD, more experimental research, extensive clinical validation, and phenotype-specific studies are needed.

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