Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

Abstract

Both extracellular vesicles (EVs) and long noncoding RNAs (lncRNAs) have been increasingly investigated as biomarkers, pathophysiological mediators, and potential therapeutics. While these two entities have often been studied separately, there are increasing reports of EV-associated lncRNA activity in processes such as oncogenesis as well as tissue repair and regeneration. Given the powerful nature and emerging translational impact of other noncoding RNAs such as microRNA (miRNA) and small interfering RNA, lncRNA therapeutics may represent a new frontier. While EVs are natural vehicles that transport and protect lncRNAs physiologically, they can also be engineered for enhanced cargo loading and therapeutic properties. In this review, we will summarize the activity of lncRNAs relevant to both tissue repair and cancer treatment and discuss the role of EVs in enabling the potential of lncRNA therapeutics. K E Y W O R D S exosomes, extracellular vesicles, lncRNA, microparticles, microvesicles lncRNAs play diverse regulatory roles in normal physiological processes. Thus, delivery of lncRNAs via EVs may help in the treatment Abbreviations: CRCs, colorectal carcinoma cells; EVs, extracellular vesicles; hAD-MSCs, human adipose-derived mesenchymal stem cells; HCAECs, human coronary artery endothelial cells; HCC, hepatocellular carcinoma cell; HDFs, human dermal fibroblasts; HDMECs, human dermal microvascular endothelial cells; lncRNA, long noncoding RNA; miRNA, microRNA; SCCs, squamous carcinoma cells.

Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets

“…In addition, they are associated with tumorigenesis and tumor microenvironment [ 175 – 177 ]. Consequently, these unique functions and biology of the EVs in cell-to-cell communications through the delivery of cargo, including mRNAs, miRNAs, and lncRNAs, make them attractive as potential therapeutics and biomarkers in various diseases [ 178 , 179 ].…”

Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

“…The majority of EV research has focused on miRNA, but other RNA species that can be found in EVs include messenger RNA (mRNA), long non-coding RNA (lncRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), RNA repeats, and circular RNA (circRNA) [ 82 , 83 , 84 , 85 , 86 ]. EV cargo can also include DNA and other genetic materials that reflect their cellular origin [ 87 , 88 ].…”

Exosomes as Drug Delivery Systems: Endogenous Nanovehicles for Treatment of Systemic Lupus Erythematosus

“…There is emerging interest in long non-coding RNAs not only as biomarkers but also as therapeutic agents due to their ability to interact with miRNAs. lncRNAs are naturally carried by EVs and are been increasingly documented as key mediators of EV biological effects [ 108 ]. Therapeutic applications of lncRNAs enclosed inside EVs span a broad range including cardiovascular, musculoskeletal, gastrointestinal and nervous system diseases, in which they have demonstrated potential use in mediating tissue regeneration and repair [ 109 , 110 ].…”