Analysis of the correlation of the expression level of hypoxia-inducible factor-1α with the glycosylation of oral squamous cell carcinoma

Objective: To investigate the correlation of the expression level of hypoxia-inducible factor-1 alpha (HIF-1 alpha) with the glycosylation of oral squamous cell carcinoma (OSCC). Methods: We conducted an immunohistochemical SP method to detect the expression levels of HIF-1 alpha and O-glycosylation-related proteins (O-linked N-acetylglucosamine [O-GlcNAc], O-GlcNAcase [OGA], and O-GlcNAc transferase [OGT]) in 30 cases of OSCC tissues that were surgically removed and confirmed by pathology in our hospital from January 2018 to July 2020. Meanwhile, the expression levels of O-GlcNAc, OGA, and OGT under the action of the HIF-1 alpha inhibitor PX-478 were detected by Western blotting in the human OSCC cell line (Tca8113 line). Results: (1) The expression of HIF-1 alpha and O-glycosylation-related proteins in OSCC was reported at an increased level. (2) The positive expression of HIF-1 alpha was associated with the age and tumor size of OSCC patients (P < 0.05); the positive expression of O-GlcNAc and OGT was related to the tumor size of OSCC patients (P < 0.05). (3) Expression of HIF-1 alpha, O-GlcNAc and OGT in OSCC tissues was positively correlated (phi correlation coefficient = 0.550). (4) Under HIF-1 alpha inhibition, a statistically significant decrease occurred in the expression levels of O-GlcNAc and OGT at a dose of 25 mu M PX-478 (P < 0.05), but a statistically significant increase occurred in OGA (P < 0.05). (5) Under the action of PX-478, there was a statistically significant and gradual decrease in the OGT content over time (P < 0.05). Conclusions: The expression of HIF-1 alpha and O-glycosylation-related proteins increases in OSCC, and the expression level increases proportionally with tumor volume. Expression of HIF-1 alpha and O-GlcNAc and OGT was positively correlated. HIF-1 alpha inhibition by PX-478 led to decreased expression levels of O-GlcNAc and OGT but the increased expression level of OGA. PX-478 can affect Tca8113 glycosylation by reducing the expression level of OGT.