Exosomes are 40–100 nm nano-sized vesicles that are released from many cell types into the extracellular space. Such vesicles are widely distributed in various body fluids. Recently, mRNAs and microRNAs (miRNAs) have been identified in exosomes, which can be taken up by neighboring or distant cells and subsequently modulate recipient cells. This suggests an active sorting mechanism of exosomal miRNAs, since the miRNA profiles of exosomes may differ from those of the parent cells. Exosomal miRNAs play an important role in disease progression, and can stimulate angiogenesis and facilitate metastasis in cancers. In this review, we will introduce the origin and the trafficking of exosomes between cells, display current research on the sorting mechanism of exosomal miRNAs, and briefly describe how exosomes and their miRNAs function in recipient cells. Finally, we will discuss the potential applications of these miRNA-containing vesicles in clinical settings.

MicroRNAs (miRNAs), a class of small, non-coding RNA molecules with gene regulatory functions, have emerged to play a critical role in the pathogenesis of a variety of diseases. Current technological advances allow accurate, high throughput profiling of miRNA abundance in different tissues. More recently, extracellular, circulating miRNAs have begun to be demonstrated as highly stable, blood-based biomarkers for diseases. Understanding the interactions between circulating miRNAs and clinical phenotypes can enhance our knowledge of complex diseases and traits. On the other hand, given the advantages of utilizing blood-based biomarkers (e.g., convenience in collecting samples), circulating miRNAs as biomarkers may improve both disease diagnosis and management. Particularly, we reviewed recent progress in identifying circulating miRNAs as biomarkers for several common inflammatory diseases including asthma, inflammatory bowel disease, and rheumatoid arthritis. Current studies showed a promising future of using circulating miRNAs in the care of inflammatory diseases.

Lung cancer has been the leading cause of cancer morbidity and mortality in recent years. Most lung cancers are often asymptomatic until advanced or metastatic stage. Therefore, looking for the diagnostic biomarker for early-stage lung cancer is quite significant. Circulating exosomal microRNAs (miRNAs) have been reported to be the diagnostic and prognostic markers of various cancers. Here, we obtained circulating exosomal miRNA repertoires of 7 early-stage lung adenocarcinoma patients including pre-operation and post-operation (LA-pre and LA-post) and 7 heathy controls (HCs) by next generation sequence (NGS) and selected miR-342-5p, miR-574-5p and miR-222-3p to validate in ampliative samples by reverse transcription-quantitative PCR (RT-qPCR). Circulating exosomal miR-342-5p, miR-574-5p and miR-222-3p not only significantly elevated in LA patients (n = 56) compared with HCs (n = 40), but also significantly decreased after tumor resection when analyzed 51 paired pre- and post-operation samples. Furthermore, miR-342-5p and miR-574-5p, but not miR-222-3p, had a significantly elevated expression level in carcinoma tissue compared with adjacent non-cancerous tissue (n = 8). The receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of combined miR-342-5p and miR-574-5p was 0.813 (95% CI: 0.7249 to 0.9009) with sensitivity and specificity of 80.0% and 73.2% respectively. In summary, circulating exosomal miR-342-5p and miR-574-5p have potential to serve as novel diagnostic biomarkers for early-stage LA.