Diagnostic and Therapeutic Roles of Extracellular Vesicles and Their Enwrapped ncRNAs in Rheumatoid Arthritis

Ya-ru Liu,1,2,* Jie-Quan Wang,3– 5,* Ling Fang,1,2 Quan Xia1,2 1Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2The Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine, Hefei, 230022, People’s Republic of China; 3Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230000, People’s Republic of China; 4Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei, 230000, People’s Republic of China; 5Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, 230000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Fang; Quan Xia, Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Email fangling@ahmu.edu.cn; xiaquan2010@163.comAbstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease whose precise pathogenesis remains mysterious. The involvement of epigenetic regulation in the pathogenesis of RA is one of the most anticipated findings, among which non-coding RNAs (ncRNAs) hold great application promise as diagnostic and therapeutic biomarkers for RA. Extracellular vesicles (EVs) are a heterogeneous group of nano-sized, membrane-enclosed vesicles that mediate intercellular communication and substance exchange, especially the transfer of ncRNAs from donor cells, thereby regulating the functional activities and biological processes of recipient cells. In light of the significant correlation between EVs, ncRNAs, and RA, we first documented expression levels of EVs and their-encapsulated ncRNAs in RA individuals, and methodically discussed their-implicated signaling pathways and phenotypic changes. The last but not least, we paied special attention to the therapeutic benefits of gene therapy reagents specifically imitating or silencing candidate ncRNAs with exosomes as carriers on RA animal models, and briefly highlighted their clinical application advantage and foreground. In conclusion, the present review may be conducive to a deeper comprehension of the diagnostic and therapeutic roles of EVs-enwrapped ncRNAs in RA, with special emphasis on exosomal ncRNAs, which may offer hints for the monitoring and treatment of RA. Keywords: rheumatoid arthritis, extracellular vesicles, non-coding RNAs, diagnostic and therapeutic role