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

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.

An appraisal of the current status of inhibition of glucose transporters as an emerging antineoplastic approach: Promising potential of new pan-GLUT inhibitors

“…Given such intimacy between various miRNAs and GLUT isoforms, there is a strong logic to utilize them in therapeutic applications. Similarly, a study on the role of MiR-218 and MiR340 in the expression of GLUT1 is demonstrated in oral squamous cell carcinoma (OSCC) (Xu et al, 2018;Shiah et al, 2021). Combinatorial use of miRNAs with other conventional GLUT1 inhibitors is also needed to be explored to circumvent GLUT at both gene expression and protein function levels.…”

Regulation of epigenetic modifications in the head and neck tumour microenvironment

“…ncRNAs, including circular RNAs (circRNAs), microRNAs (miRNAs), and lncRNAs, interact with the components of the TME, thereby affecting tumorigenesis and progression (Table S1) (86)(87)(88). These ncRNAs, which are enriched in exosomes of CAFs, are transmitted to the cancer cells to regulate their biological characteristics.…”

The prognostic value of MicroRNAs associated with fatty acid metabolism in head and neck squamous cell carcinoma

“…Head and neck squamous cell carcinoma (HNSCC), one of the most prevalent malignancies in the world, is a cancer of the squamous epithelium that lines the head and neck organs, such as the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, paranasal sinuses, nasal cavity, and salivary glands with poor outcomes and survival rates ( Shiah et al, 2021 ). However, palliative care is being considered as a systematic therapy for patients with recurrent or spread HNSCC.…”

“…In the last 10 years, it has been shown that microRNAs play an important role in the development of HNSCC cancer and its spread ( Qiu et al, 2021 ; Shiah et al, 2021 ; Yang et al, 2019 ; Yu et al, 2019 ). This makes them good candidates for biomarkers that can predict the biological activity of HNSCC.…”