SDHB reduction promotes oral lichen planus by impairing mitochondrial respiratory function.

BACKGROUND

Oral lichen planus (OLP) is a type of chronic inflammatory disorder, which represents a potential risk of malignant transformation. Understanding the mechanism of OLP-related malignant transformation could reduce the risk of cancer. Accumulating evidence indicates that the expression of succinate dehydrogenase enzyme B (SDHB) is associated with the carcinogenesis of oral squamous cell carcinoma (OSCC). However, the function and underlying mechanism of SDHB in OLP remains unknown.

METHODS

In this study, we examined the expression of SDHB in tissues from OLP patients and normal oral mucosa (NOM) through immunohistochemical (IHC) staining, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blot (WB). Adenosine triphosphate (ATP) assay, reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) assay, and glucose uptake assay were used to explore the function of SDHB in mitochondrial injury and bioenergetic changes in OLP cell model and SDHB-overexpressing cells.

RESULTS

In current study, we found that the messenger RNA (mRNA) and protein expression of SDHB was significantly decreased in OLP patients, accompanied by the accumulation of succinate. In the lipopolysaccharide (LPS) or CoCl2-stimulated OLP cell model, the expression of SDHB was decreased along with treatment time and concentration. Mechanistically, decreased SDHB enhanced hypoxia-inducible factor (HIF)-1α activity, induced mitochondrial injury, bioenergetic changes, and cytokine release. Overexpression of SDHB could reverse the above biological process and switch bioenergetic metabolism during OLP process.

CONCLUSIONS

Our study suggests that SDHB reduction promotes OLP by impairing mitochondrial respiratory function.