SDHB reduction promotes oral lichen planus by impairing mitochondrial respiratory function

Hui Zhang; Beiyun Xu; Jin Liu; Bin Guo; Hongying Sun; Qiaozhen Yang

doi:10.21037/atm-22-5999

SDHB reduction promotes oral lichen planus by impairing mitochondrial respiratory function

Ann Transl Med. 2022 Dec;10(24):1367. doi: 10.21037/atm-22-5999.

Authors

Hui Zhang¹, Beiyun Xu¹, Jin Liu¹, Bin Guo², Hongying Sun¹, Qiaozhen Yang¹

Affiliations

¹ Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, China.
² School of Life Sciences, Fudan University, Shanghai, China.

Abstract

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.

Keywords: Succinate dehydrogenase enzyme B (SDHB); glycolytic metabolism; hypoxia-inducible factor-1α (HIF-1α); mitochondrial respiratory function; oral lichen planus (OLP).