Abstract
Simple SummaryHead and neck squamous cell carcinomas (HNSCCs) are highly heterogeneous human malignancies associated with genetic and environmental factors. In HNSCCs, cancer stem cells (CSCs) provide the plasticity for cancer cell progression, metastasis, therapeutic resistance, and recurrence. During carcinogenesis, microRNAs (miRNAs) play important roles in regulating the maintenance and acquisition of cancer stem cell features. Therefore, in this review, we summarize the roles of miRNAs in regulating the cancer stemness of HNSCCs to provide potential therapeutic applications.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.
Highlights
Cancer is responsible for about 30% of all premature deaths from non-communicable diseases (NCDs) in adults aged approximately 30–69 years [1]
In laryngeal SCCs (LSCCs), miR-98 was shown significantly reduced in both clinical specimens and cell lines, and miR-98 directly targeted HMGA2-POSTN signaling and suppressed cell migration, metastasis, invasion, and epithelial-to-mesenchymal transition (EMT)-TFs of Snail family transcriptional repressor 1 (SNAI1) and twist family bHLH transcription factor 1 (Twist1), as well as SC-like features [216]
Conclusions miRNAs can function as cancer suppressors or oncogenes, or even exhibit dual roles during cancer development, depending on the different cancer types or tumorigenesis stage. miRNAs are critical to tumor initiation, progression, metastasis, EMT, and chemoresistance via regulating cancer stem cells (CSCs) functions. miRNAs regulate important EMT-TFs and signaling pathways and modulate the tumor microenvironment (TME) to sustain and enhance cancer stemness
Summary
Cancer is responsible for about 30% of all premature deaths from non-communicable diseases (NCDs) in adults aged approximately 30–69 years [1]. Head and neck squamous cell carcinomas (HNSCCs) are epithelial malignancies located in the oral cavity, nasal cavity, pharynx (nasopharynx, oropharynx, and hypopharynx), and larynx [3,4]. HNSCC subtypes include oral SCCs (OSCCs), laryngeal SCCs (LSCCs), nasopharyngeal carcinomas (NPCs), and oropharyngeal SCCs (OPSCCs) [5,6]. Advanced approaches have been developed by applying immunotherapy or combined immunotherapy treatment to treat resistant and recurrent cases [13]. Cancer stem cells (CSCs) are small populations of cancer cells and are well-known for their association with cancer resistance, relapse, tumorigenesis, and poor clinical outcomes in HNSCCs, which has promoted the development of novel and effective therapeutic protocols for better clinical outcomes [5,14].
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