PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation and thus affect the malignant progression of esophageal squamous cell carcinoma.

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the digestive tract with complex pathogenesis. There is a pressing need to search for ESCC targeted therapy sites and explore its pathogenesis. Prothymosin alpha () is abnormally expressed in numerous tumors and has a significant regulatory effect on tumor malignant progression. However, the regulatory role and mechanism of in ESCC have not yet been reported.

METHODS

We first detected the expression in ESCC patients, subcutaneous tumor xenograft models of ESCC, and ESCC cells. Subsequently, expression in ESCC cells was inhibited by cell transfection, and cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, and Western blot. A dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was used to detect reactive oxygen species (ROS) level in cells, and MitoSOX fluorescent probe, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining, mitochondrial complex kit, and Western blot were used to detect the expression of mitochondrial oxidative phosphorylation. Next, the combination between and high mobility group box 1 () was detected using Co-immunoprecipitation (co-IP) and immunofluorescence (IF) techniques. Finally, the expression of was inhibited and the expression of was overexpressed in cells via cell transfection, and the regulatory effect of and binding on mitochondrial oxidative phosphorylation in ESCC was determined through related experiments.

RESULTS

The expression of in ESCC was abnormally elevated. The inhibition of expression in ESCC cells significantly decreased the activity of ESCC cells and increased their apoptosis. Moreover, interference with can induce ROS aggregation in ESCC cells by inhibiting mitochondrial oxidative phosphorylation, which may be achieved by binding to .

CONCLUSIONS

binds to to regulate mitochondrial oxidative phosphorylation, thereby affecting the malignant progression of ESCC.