Regulation of MicroRNA Biogenesis and Its Implications in Idiopathic Pulmonary Fibrosis: A Narrative Review

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease characterized by excessive deposition of extracellular matrix and progressive destruction of the lung architecture. Repeated epithelial injury and aberrant tissue repair are strongly associated with its pathogenesis; however, the molecular mechanisms underlying disease progression remain incompletely understood. Altered microRNA (miRNA) expression has been extensively associated with IPF, but comparatively little attention has been given to the mechanisms regulating miRNA maturation and processing during pulmonary fibrosis. Objective: In this narrative review, we aimed to describe the relationship between IPF pathogenesis and alterations in miRNA maturation, with particular emphasis on post-transcriptional mechanisms that may disrupt the production and function of mature miRNAs. Methods: We conducted a narrative review of the available literature using PubMed, Scopus, and Google Scholar. No specific time frame was established because of the limited number of studies directly addressing miRNA maturation in IPF. Original research articles were prioritized, while relevant studies describing miRNA maturation mechanisms in other biological and disease contexts were also considered to provide mechanistic insight. Results: The available evidence suggests that alterations in miRNA maturation may contribute to miRNA dysregulation in IPF beyond changes in transcriptional control. Disruption of the Drosha/DGCR8 microprocessor complex, altered Dicer-dependent processing, and post-transcriptional modifications of miRNA precursors may affect the production of mature miRNAs. In addition, adenosine-to-inosine editing mediated by adenosine deaminases acting on RNA (ADARs) may modify miRNA sequences and influence their maturation, stability, and target selection. Mechanotransduction-associated pathways, including Hippo/YAP signaling, may further interfere with the miRNA-processing machinery. These alterations may contribute to the persistent dysregu-lation of antifibrotic miRNAs, including miR-29, thereby promoting extracellular matrix accumulation and sustaining profibrotic signaling. Conclusions: Although evidence directly linking defects in miRNA maturation to IPF remains limited, available findings support the hypothesis that alterations in post-transcriptional miRNA processing represent an additional regulatory layer contributing to pulmonary fibrosis. Further experimental studies are needed to determine how specific alterations in miRNA maturation and editing contribute to IPF pathogenesis and whether components of the miRNA-processing machinery may represent potential therapeutic targets.