The Role of Non-coding RNAs in Connective Tissue Diseases: Diagnostic and Therapeutic Potential of miRNAs, lncRNAs and circRNAs.

Connective tissue diseases (CTDs) are a heterogeneous group of disorders characterized by structural and functional impairment of the extracellular matrix, manifesting primarily as autoimmune, heritable or degenerative conditions such as systemic lupus erythematosus (SLE), osteogenesis imperfecta (OI) and abdominal aortic aneurysm (AAA). In SLE, lupus nephritis remains a leading cause of morbidity and a major determinant of long-term outcomes. Recent advances in transcriptomics and epigenomics have revealed non-coding RNAs (ncRNAs), including microRNA (miRNAs), long non-coding RNA (lncRNAs) and circular RNA (circRNAs), as pivotal regulators of gene expression, immune responses and tissue remodeling. Their tissue-specific expression profiles, molecular stability and involvement in key pathogenic pathways make them promising candidates for diagnostic biomarkers and therapeutic interventions. In this review, we summarize current knowledge of the roles of ncRNAs in CTDs, focusing on their regulatory mechanisms in immune dysregulation, extracellular matrix homeostasis and cell fate determination. Furthermore, we highlight their diagnostic potential in liquid biopsy approaches and discuss therapeutic strategies employing RNA mimics, inhibitors and antisense oligonucleotides. Finally, we address future perspectives, including the integration of multi-omics approaches and targeted delivery systems, which may accelerate the translation of ncRNA-based therapies into clinical practice.