Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis

Liver and cardiac fibrosis are critical drivers of chronic organ dysfunction, characterised by fibroblast activation, excessive extracellular matrix deposition, and inflammation. While these fibrotic processes are initiated by distinct triggers and monitored by organ-specific biomarkers, emerging evidence reveals both shared and unique regulatory networks, particularly involving non-coding RNAs (ncRNAs). This review focuses on the roles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), such as miR-21, miR-22, miR-29, miR-34a, miR-122, miR-133a, miR-210, miR-214, H19, MALAT1, MEG3, NEAT1, and circHIPK3, in modulating key fibrotic pathways including TGF-β/SMAD signalling, oxidative stress, and extracellular matrix remodelling in both hepatic and cardiac tissues. Some ncRNAs exhibit convergent regulatory functions across both organs, while others demonstrate divergent or context-dependent effects within and between tissues. Furthermore, circulating ncRNAs, potentially transferred via extracellular vesicles (EVs), hold potential as minimally invasive biomarkers for early detection of combined cardio-hepatic fibrosis, as exemplified in conditions like Fontan circulation, though extensive validation in large, prospective cohorts is essential. This article summarises established clinical biomarkers, discusses the ncRNA-mediated mechanisms operating in liver and heart fibrosis, distinguishing shared, divergent, and mixed evidence, and explores their translational potential in diagnostics and experimental therapeutics. Finally, it addresses remaining challenges and outlines future directions, emphasising multi-omic integration, longitudinal ncRNA profiling, and mechanistic validation to advance precision management of fibrotic diseases.