MicroRNAs: Their Role in Metabolism, Tumor Microenvironment, and Therapeutic Implications in Head and Neck Squamous Cell Carcinoma

SIMPLE SUMMARY: Head and neck squamous cell carcinoma (HNSCC), which arises from the oral epithelium, is one of the most common cancers worldwide. Despite excellent diagnosis and treatment improvements, the mortality rate associated with HNSCC is still extremely high. Current data suggest that dysregulation of exosomes and metabolic abnormalities are involved in the initiation and progression of HNSCC. Thus, approaches for targeting exosomes in the tumor microenvironment and metabolic reprogramming pathways represent potential therapeutic strategies. Moreover, some miRNAs are thought to have significant functions in regulating the progression of HNSCC. The present article aims to summarize the current knowledge concerning the important miRNAs in both exosomes and cancer metabolism, as well as discuss future perspectives regarding their future diagnostic potential and treatment recommendations. ABSTRACT: MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that negatively regulate gene expression by binding to target mRNAs. Deregulated miRNAs can act as either oncogenic miRNAs or tumor suppressor miRNAs in controlling proliferation, differentiation, apoptosis, metastasis, epithelial–mesenchymal transition, and immune responses, which are all involved in the carcinogenesis process of HNSCC. Recent findings have shown that metabolic reprogramming is an important hallmark of cancer, which is necessary for malignant transformation and tumor development. Some reprogrammed metabolisms are believed to be required for HNSCC against an unfavorable tumor microenvironment (TME). The TME is composed of various cell types embedded in the altered extracellular matrix, among which exosomes, secreted by cancer cells, are one of the most important factors. Tumor-derived exosomes reshape the tumor microenvironment and play a crucial role in cell-to-cell communication during HNSCC development. Exosomes encapsulate many biomolecules, including miRNAs, circulate in body fluids, and can transmit intercellular regulatory messages to nearby and distant sites, which indicates that exosomal miRNAs have the potential to become non-invasive biomarkers. This review aims to clarify the functions of diverse miRNAs in HNSCC metabolic reprogramming and tumor-derived exosomes. In addition, it also emphasizes the potential role of miRNA as a biomarker in the diagnosis, prognosis, and treatment of HNSCC cancer.