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

Xiaoliang Xu; Hui Liu; Ran Wu; Weiwen Zuo; Tiantao Wang; Dong Chen

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

Am J Transl Res. 2021 Jun 15;13(6):6686-6693. eCollection 2021.

Authors

Xiaoliang Xu¹, Hui Liu², Ran Wu², Weiwen Zuo³, Tiantao Wang⁴, Dong Chen¹

Affiliations

¹ Department of Dental, The Second Hospital of Tangshan Tangshan, China.
² Dental Department, North China University of Science and Technology Affiliated Hospital Tangshan, China.
³ Stormotologry Department, Tangshan Vocational and Technical College Tangshan, China.
⁴ School of Basic Medicine Science, North China University of Science and Technology Tangshan, China.

PMID: 34306413
PMCID: PMC8290824

Abstract

Objective: To investigate the correlation of the expression level of hypoxia-inducible factor-1α (HIF-1α) with the glycosylation of oral squamous cell carcinoma (OSCC).

Methods: We conducted an immunohistochemical SP method to detect the expression levels of HIF-1α 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-1α inhibitor PX-478 were detected by Western blotting in the human OSCC cell line (Tca8113 line).

Results: ① The expression of HIF-1α and O-glycosylation-related proteins in OSCC was reported at an increased level. ② The positive expression of HIF-1α 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-1α, O-GlcNAc and OGT in OSCC tissues was positively correlated (φcorrelation coefficient = 0.550). ④ Under HIF-1α inhibition, a statistically significant decrease occurred in the expression levels of O-GlcNAc and OGT at a dose of 25 μM 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-1α and O-glycosylation-related proteins increases in OSCC, and the expression level increases proportionally with tumor volume. Expression of HIF-1α and O-GlcNAc and OGT was positively correlated. HIF-1α 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.

Keywords: Hypoxia-inducible factor-1α; O-glycosylation; correlation; expression level; oral squamous cell carcinoma.