PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma

Abstract

Background/objective: Accumulated evidence has demonstrated that aerobic glycolysis serves as a regulator of tumor cell growth, invasion, and angiogenesis. Herein, we explored the role of protein disulfide isomerase family 6 (PDIA6) in the aerobic glycolysis and the progression of oral squamous cell carcinoma (OSCC).

Methods: The expression pattern of PDIA6 in OSCC tissues was determined by qPCR and western blotting. Lentivirus and small interfering RNAs (siRNAs) were introduced into cells to upregulate and downregulate PDIA6 expression. CCK-8, flow cytometry, transwell, and xenotransplantation models were applied to detect cell proliferation, apoptosis, migration, invasion, and tumorigenesis, respectively.

Results: A high expression pattern of PDIA6 was observed in OSCC tissues, which was closely associated with lower overall survival and malignant clinical features in OSCC. Compared with the control group, overexpression of PDIA6 induced significant enhancements in cell growth, migration, invasiveness, and tumorigenesis and decreased cell apoptosis, while knockdown of PDIA6 caused opposite results. In addition, overexpression of PDIA6 increased glucose consumption, lactate production, and ATP level in OSCC cells.

Conclusion: This study demonstrated that PDIA6 expression was elevated in OSCC tissues, and overexpression of it promoted aerobic glycolysis and OSCC progression.

Keywords: Aerobic glycolysis; Migration; PDIA6; Proliferation; Tumorigenesis.

Fig. 1

PDIA6 was highly expressed in OSCC tissues and predicted with poor prognosis. a The expression levels of PDIA6 mRNA were detected in 58 matched OSCC tissues and the adjacent normal tissues were determined by qPCR. b The protein levels of PDIA6 in 4 paired OSCC tissues and the adjacent normal tissues were determined by western blotting assay. c Kaplan-Meier analysis of the relationship between PDIA6 mRNA levels and the overall survival of OSCC patients (*p < 0.05)

Fig. 2

Assessment of PDIA6 role in cell proliferation and apoptosis in SCC9 and Cal27 cells. SCC9 and Cal27 cells were infected/transfected with OE-PDIA6, OE-NC, si-PDIA6, or si-NC, and then collected for detection. a, b qPCR and western blotting assays were applied to detect the mRNA and protein levels of PDIA6, respectively. c, d CCK-8 assay was applied for proliferation detection. e, f Flow cytometry was performed for cell apoptosis detection (n = 3, *p < 0.05, OE-PDIA6 group vs. OE-NC group; ^#p < 0.05, si-PDIA6 group vs. si-NC group)

Fig. 3

Assessment of PDIA6 role in cell migration and invasion in SCC9 and Cal27 cells. SCC9 and Cal27 cells were infected/transfected with OE-PDIA6, OE-NC, si-PDIA6, or si-NC, and then submitted to transwell chambers assay to detect a cell migration and b invasion (n = 3, *p < 0.05, OE-PDIA6 group vs. OE-NC group; ^#p < 0.05, si-PDIA6 group vs. si-NC group)

Fig. 4

Assessment of PDIA6 role in aerobic glycolysis in SCC9 and Cal27 cells. SCC9 and Cal27 cells infected/transfected with OE-PDIA6, OE-NC, si-PDIA6, or si-NC were collected and submitted to the detection of a glucose consumption, b lactate production, and c ATP level (n = 3, *p < 0.05, OE-PDIA6 group vs. OE-NC group; ^#p < 0.05, si-PDIA6 group vs. si-NC group)

Fig. 5

Overexpression of PDIA6 promoted in vivo tumor formation of SCC9 cells. a Tumor weights and b volume were assessed in mice injected with OE-NC or OE-PDIA6 stably transfected SCC9 cells (*p < 0.05, OE-PDIA6 group vs. OE-NC group)