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.

Background Head and neck squamous cell carcinoma (HNSCC) remains an unmet medical challenge. Metabolic reprogramming is a hallmark of diverse cancers, including HNSCC. Methods We investigated the metabolic profile in HNSCC by using The Cancer Genome Atlas (TCGA) (n = 481) and Gene Expression Omnibus (GEO) (n = 97) databases. The metabolic stratification of HNSCC samples was identified by using unsupervised k-means clustering. We analyzed the correlations of the metabolic subtypes in HNSCC with featured genomic alterations and known HNSCC subtypes. We further validated the metabolism-related subtypes based on features of ENO1, PFKFB3, NSDHL and SQLE expression in HNSCC by Immunohistochemistry. In addition, genomic characteristics of tumor metabolism that varied among different cancer types were confirmed. Results Based on the median expression of coexpressed cholesterogenic and glycolytic genes, HNSCC subtypes were identified, including glycolytic, cholesterogenic, quiescent and mixed subtypes. The quiescent subtype was associated with the longest survival and was distributed in stage I and G1 HNSCC. Mutation analysis of HNSCC genes indicated that TP53 has the highest mutation frequency. The CDKN2A mutation frequency has the most significant differences amongst these four subtypes. There is good overlap between our metabolic subtypes and the HNSCC subtype. Conclusion The four metabolic subtypes were successfully determined in HNSCC. Compared to the quiescent subtype, glycolytic, cholesterogenic and mixed subtypes had significantly worse outcome, which might offer guidelines for developing a novel treatment strategy for HNSCC.

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.