Roles of microRNAs in Regulating Cancer Stemness in Head and Neck Cancers

Abstract

Head and neck squamous cell carcinomas (HNSCCs) are epithelial malignancies with 5-year overall survival rates of approximately 40–50%. Emerging evidence indicates that a small population of cells in HNSCC patients, named cancer stem cells (CSCs), play vital roles in the processes of tumor initiation, progression, metastasis, immune evasion, chemo-/radioresistance, and recurrence. The acquisition of stem-like properties of cancer cells further provides cellular plasticity for stress adaptation and contributes to therapeutic resistance, resulting in a worse clinical outcome. Thus, targeting cancer stemness is fundamental for cancer treatment. MicroRNAs (miRNAs) are known to regulate stem cell features in the development and tissue regeneration through a miRNA–target interactive network. In HNSCCs, miRNAs act as tumor suppressors and/or oncogenes to modulate cancer stemness and therapeutic efficacy by regulating the CSC-specific tumor microenvironment (TME) and signaling pathways, such as epithelial-to-mesenchymal transition (EMT), Wnt/β-catenin signaling, and epidermal growth factor receptor (EGFR) or insulin-like growth factor 1 receptor (IGF1R) signaling pathways. Owing to a deeper understanding of disease-relevant miRNAs and advances in in vivo delivery systems, the administration of miRNA-based therapeutics is feasible and safe in humans, with encouraging efficacy results in early-phase clinical trials. In this review, we summarize the present findings to better understand the mechanical actions of miRNAs in maintaining CSCs and acquiring the stem-like features of cancer cells during HNSCC pathogenesis.

Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs

“…Furthermore, it has been shown that miRNA signatures can serve as biomarkers for diagnosis and prognosis, and for predicting a patient’s response to treatment [ 24 , 25 ]. There is also enough evidence to suggest that a significant number of miRNAs are abnormally expressed during HNSCC tumorigenesis and progression, either functioning as OncomiRs or as tumor suppressors [ 26 ].…”

Advancement in Cancer Stem Cell Biology and Precision Medicine—Review Article Head and Neck Cancer Stem Cell Plasticity and the Tumor Microenvironment

“…Epigenetic and post-translational alterations provide additional mechanisms for cancer stem cell reprogramming. Dong et al demonstrated the importance of super enhancers in promoting cancer stem cells ( Dong et al, 2021 ) and there is mounting evidence for the role of microRNAs in cancer stem call regulation ( Bourguignon et al, 2012 ; Barlak et al, 2020 ; Fitriana et al, 2021 ). These necessary metabolic and other perturbations are often driven by interactions with neighboring cells in the tumor microenvironment.…”

p53 Modulates Radiosensitivity in Head and Neck Cancers—From Classic to Future Horizons

“…Inhibition of PDZ-binding kinase (PBK) and p53 activation has the effect of radiosensitization of nasopharyngeal tumors, a process regulated by miR-372. miR-200 is involved in reducing EMT mediated by p53 [ 87 , 88 , 89 ].…”