Oral squamous cell carcinoma accounts for 95% of human head and neck squamous cell carcinoma cases. It is highly malignant and aggressive, with a poor prognosis and a 5-year survival rate of <50%. In recent years, basic and clinical studies have been performed on the role of the mitogen-activated protein kinase (MAPK) signaling pathway in oral cancer. The MAPK signaling pathway is activated in over 50% of human oral cancer cases. Herein, we review research progress on the MAPK signaling pathway and its potential therapeutic mechanisms and discuss its molecular targeting to explore its potential as a therapeutic strategy for oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a type of malignancy with high mortality, leading to poor prognosis worldwide. However, the molecular mechanisms underlying OSCC carcinogenesis have not been fully understood. Recently, the discovery and characterization of long non-coding RNAs (lncRNAs) have revealed their regulatory importance in OSCC. Abnormal expression of lncRNAs has been broadly implicated in the initiation and progress of tumors. In this review, we summarize the functions and molecular mechanisms regarding these lncRNAs in OSCC. In addition, we highlight the crosstalk between lncRNA and tumor microenvironment (TME), and discuss the potential applications of lncRNAs as diagnostic and prognostic tools and therapeutic targets in OSCC. Notably, we also discuss lncRNA-targeted therapeutic techniques including CRISPR-Cas9 as well as immune checkpoint therapies to target lncRNA and the PD-1/PD-L1 axis. Therefore, this review presents the future perspectives of lncRNAs in OSCC therapy, but more research is needed to allow the applications of these findings to the clinic.

The polycomb group (PcG) comprises a set of proteins that exert epigenetic regulatory effects and play crucial roles in diverse biological processes, ranging from pluripotency and development to carcinogenesis. Among these proteins, enhancer of zeste homolog 2 (EZH2) stands out as a catalytic component of polycomb repressive complex 2 (PRC2), which plays a role in regulating the expression of homologous (Hox) genes and initial stages of x chromosome inactivation. In numerous human cancers, including head and neck squamous cell carcinoma (HNSCC), EZH2 is frequently overexpressed or activated and has been identified as a negative prognostic factor. Notably, EZH2 emerges as a significant gene involved in regulating the STAT3/HOTAIR axis, influencing HNSCC proliferation, differentiation, and promoting metastasis by modulating related oncogenes in oral cancer. Currently, various small molecule compounds have been developed as inhibitors specifically targeting EZH2 and have gained approval for treating refractory tumors. In this review, we delve into the epigenetic regulation mediated by EZH2/PRC2 in HNSCC, with a specific focus on exploring the potential roles and mechanisms of EZH2, its crucial contribution to targeted drug therapy, and its association with cancer markers and epithelial–mesenchymal transition. Furthermore, we aim to unravel its potential as a therapeutic strategy for oral squamous cell carcinoma.

Recent studies have demonstrated an important role for mitotically associated long non-coding RNA (MANCR) in carcinogenesis and cancer progression, but its function has not been elucidated in head and neck squamous cell carcinoma (HNSCC). In this study, we identified differentially expressed MANCR from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases across 24 cancer types and included 546 HNSCC patients. Furthermore, high expression of MANCR was verified in HNSCC cell lines and tissue by using real-time quantitative PCR (RT-qPCR) analysis. The Kaplan–Meier analysis showed a worse prognosis with higher levels of MANCR for HNSCC. The univariate Cox regression and multivariate Cox regression analyses revealed that MANCR was a high-risk factor in patients with HNSCC. Thereafter, we carried out the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. It was indicated that MANCR participates in axonogenesis and ECM-receptor interaction. Further enrichment analysis demonstrated that the expression of MANCR was positively correlated with the T gamma delta (tgd) cells, neutrophils, and Th1 cells, and negatively correlated with the infiltration of B cells, CD8 T cells, and T cells in HNSCC. In addition, in vitro experiments showed that knockdown of MANCR in HNSCC cells markedly inhibited cell proliferation, migration, and invasion. We find that MANCR was elevated in HNSCC and promoted the malignant progression of HNSCC. MANCR may serve as a potential biomarker in prognostic implications for HNSCC patients. The positive correlation between MANCR and immune infiltration cells may provide novel therapeutic targets and personalized immune-based cancer therapy for HNSCC.