Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

Abstract

Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are closely related to a variety of biological and functional aspects of human health. When the exosomal ncRNAs undergo tissue-specific changes due to diverse internal or external disorders, they can cause tissue dysfunction, aging, and diseases. In this review, we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases. In addition, we explore the current knowledge on the roles of exosomal miRNAs, lncRNAs, and circRNAs in human health and diseases, including cancers, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and infectious diseases, to determine their potential implication in biomarker identification and therapeutic exploration.

Fig. 1

Timeline of the discovery and research history of ncRNAs in human health and diseases. Key discoveries are highlighted. XIST X (inactive)-specific transcript, RNAi RNA interference, piRNA PIWI-interacting RNA, HOTAIR HOX transcript antisense RNA, ENCODE Encyclopedia of DNA Elements

Fig. 2

The potential regulatory mechanisms of exosomes in human diseases. Several mechanisms of the occurrence of human diseases are modulated by exosomes, including immune response, oxidative stress, autophagy, gut microbe, and cell cycle. This figure was created with the aid of Servier Medical Art (https://smart.servier.com/). ROS reactive oxygen species, HSP heat shock protein, AKT3 AKT serine/threonine kinase 3, IR insulin resistance, CDK cyclin-dependent kinase, NK natural killer, DC dendritic cell

Fig. 3

Different mechanisms underlying the stability of extracellular ncRNAs. NcRNAs can be protected from harsh extracellular environment through extracellular vesicles encapsulation (such as exosomes and microvesicles), ribonucleoprotein (RNP) complex formation, and high-density lipoprotein (HDL) transportation. Moreover, some extracellular RNA fragments that generate from non-vesicular ncRNAs in extracellular space can form self-protecting dimers. The source of these non-vesicular RNAs remains uncertain. This figure was created with the aid of Servier Medical Art (https://smart.servier.com/). MVB multivesicular bodies, RBPs RNA-binding protein, rRFs rRNA-derived fragments

Fig. 4

The roles of exosomal ncRNAs in human diseases. The figure showed examples of human diseases where exosomal ncRNAs exert pivotal function. This figure was created with the aid of Servier Medical Art (https://smart.servier.com/)

Fig. 5

The roles of exosomal ncRNAs in cancer. Exosomal ncRNAs play a role in cancers, including EMT, proliferation, angiogenesis, metastasis, drug resistance, and immune response. This figure was created with the aid of Servier Medical Art (https://smart.servier.com/). EMT epithelial-mesenchymal transition, DC dendritic cell, NK natural killer

Fig. 6

The role of exosomal ncRNA in the pathological process of metabolic diseases. Exosomes secreted by different tissues can be released into the circulation and transported to other organs, where they are internalized by recipient cells, mediating metabolic regulation. This figure was created with the aid of Servier Medical Art (https://smart.servier.com/)

Fig. 7

Exosomal ncRNA-based therapeutics in human diseases. Endogenous (pre-loading cargoes into donor cells followed by exosomal cargo release) or exogenous (directly loading cargoes into exosomes after their production or isolation) loading of ncRNAs or their inhibitors into exosomes exhibits significant therapeutic potential. ASO antisense oligonucleotide. This figure was created with the aid of Servier Medical Art (https://smart.servier.com/)