Aerobic glycolysis is the main pathway for energy metabolism in cancer cells. It provides energy and biosynthetic substances for tumor progression and metastasis by increasing lactate production. Lactate dehydrogenase A (LDHA) promotes glycolysis process by catalyzing the conversion of pyruvate to lactate. Despite LDHA exhibiting carcinogenesis in various cancers, its role in oral squamous cell carcinoma (OSCC) remains unclear. This study demonstrated that LDHA was over-expressed in both OSCC tissues and cell lines, and was significantly associated with lower overall survival rates in patients with OSCC. Using weighted gene correlation network analysis and gene set enrichment analysis for the gene expression data of patients with OSCC (obtained from The Cancer Genome Atlas database), a close association was identified between epithelial–mesenchymal transition (EMT) and LDHA in promoting OSCC progression. The knockdown of LDHA suppressed EMT, cell proliferation, and migration and invasion of OSCC cells in vitro. Moreover, the silencing of LDHA inhibited tumor growth in vivo. Oxamate, as a competitive LDHA inhibitor, was also suppressed diverse malignant biocharacteristics of OSCC cells. Our findings reveal that LDHA acts as an oncogene to promote malignant progression of OSCC by facilitating glycolysis and EMT, and LDHA may be a potential anticancer therapeutic target.

Lymphovascular invasion (LVI) has been reported as a predictor of prognosis in multiple cancers. The aim of this meta-analysis was to investigate the potential value of LVI as a prognostic predictor of oral squamous cell carcinoma (OSCC). To identify relevant studies, PubMed, Embase, Web of Science, and Cochrane Library database were searched from inception to October 2020. All studies exploring the association of LVI with overall survival (OS), disease-specific survival (DSS), or disease-free survival (DFS) and lymph node metastasis (LNM) were identified. Pooled odds ratios for LNM and hazard ratios for survival were calculated using fixed effects or random effects models. Thirty-six studies involving 17,109 patients with OSCC were included and further analyzed. The results showed that positive LVI was significantly associated with LNM and worse survival in patients with OSCC. Moreover, positive LVI was correlated with LNM in patients with early stage OSCC. These findings indicate that LVI may serve as a prognostic predictor for the metastasis and prognosis of OSCC and could be considered a routine pathologic examination in clinical work.

Although it has been previously documented that a hypoxic environment can promote glycolysis and the malignant progression of oral squamous cell carcinoma (OSCC) cells, the specific underlying mechanism remains unclear. Phosphoglycerate kinase 1 (PGK1) has been previously reported to serve an important role in tumor metabolism. The aim of the present study was to investigate the effects of hypoxia and PGK1 on glycolysis, stem cell‑like properties and epithelial‑mesenchymal transition (EMT) in OSCC cells. Cell Counting Kit‑8 assays were performed to examine tumor cell viability under hypoxic conditions. Sphere formation, immunohistochemistry, western blotting, Transwell assays and mouse xenograft studies were performed to assess the biological effects of PGK1. Under hypoxic conditions, phosphoglycerate PGK1 expression was found to be upregulated, which resulted in the potentiation of stem cell‑like properties and enhancement of EMT. However, PGK1 knockdown reversed hypoxia‑mediated glycolysis, stem cell‑like properties, EMT in addition to inhibiting OSCC cell invasion and migration. PGK1 knockdown also inhibited tumour growth, whilst the overexpression of PGK1 was demonstrated to promote tumour growth in mouse xenograft models in vivo. Downstream, activation of the AKT signalling pathway reversed the series of changes induced by PGK1 knockdown. PGK1 expression was found to be upregulated in human OSCC tissues, which was associated with the pathological differentiation of tumours and lymph node metastasis. To conclude, results from the present study demonstrate that hypoxia can increase PGK1 expression, resulting in the promotion of glycolysis, enhancing stem cell‑like properties and EMT by activating AKT signalling in OSCC.