More than a Bubble: Extracellular Vesicle microRNAs in Head and Neck Squamous Cell Carcinoma

SIMPLE SUMMARY: Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal disease. Despite diagnostic and therapeutic advances, the overall survival of patients with advanced HNSCC remains poor. Recently, microRNAs in extracellular vesicles (EV-miRNAs) have been proposed as essential regulatory molecules involved in HNSCC. EV-miRNAs may serve as disease biomarkers and represent a novel therapeutic target. This review summarizes the current understanding of the role of EV-miRNAs in HNSCC as well as their potential future clinical applications. ABSTRACT: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play a pivotal regulatory role in a broad variety of biological processes. Dysregulation of miRNAs is associated with several human diseases, particularly cancer. Extracellular vesicles (EVs) are crucial components in intercellular communication. As part of the cargo of EVs, miRNAs are involved in EV-mediated cell-to-cell interactions, including promotion or suppression of tumor development. The knowledge on the molecular mechanisms and clinical importance of EV-miRNAs in head and neck squamous cell carcinoma (HNSCC) has rapidly grown over the past years. In the present review, the current understanding regarding the effect of EV-miRNAs on HNSCC tumorigenesis is summarized, which includes effects on tumor proliferation, angiogenesis, invasion and metastasis, the tumor microenvironment, immune modulation, and treatment resistance. EV-miRNA-based biomarkers in liquid biopsies such as blood and saliva may open up new possibilities for employing EV-miRNAs for screening and early diagnostics as well as disease monitoring. Future perspectives include the promise of EV-miRNAs as a novel therapeutic target.