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

Abstract

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 (PTMA) is abnormally expressed in numerous tumors and has a significant regulatory effect on tumor malignant progression. However, the regulatory role and mechanism of PTMA in ESCC have not yet been reported. Methods: We first detected the PTMA expression in ESCC patients, subcutaneous tumor xenograft models of ESCC, and ESCC cells. Subsequently, PTMA 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 PTMA and high mobility group box 1 (HMGB1) was detected using Co-immunoprecipitation (co-IP) and immunofluorescence (IF) techniques. Finally, the expression of PTMA was inhibited and the expression of HMGB1 was overexpressed in cells via cell transfection, and the regulatory effect of PTMA and HMGB1 binding on mitochondrial oxidative phosphorylation in ESCC was determined through related experiments. Results: The expression of PTMA in ESCC was abnormally elevated. The inhibition of PTMA expression in ESCC cells significantly decreased the activity of ESCC cells and increased their apoptosis. Moreover, interference with PTMA can induce ROS aggregation in ESCC cells by inhibiting mitochondrial oxidative phosphorylation, which may be achieved by binding to HMGB1. Conclusions: PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation, thereby affecting the malignant progression of ESCC.

Presenilin-1-Derived Circular RNAs: Neglected Epigenetic Regulators with Various Functions in Alzheimer’s Disease

“…It encodes a protein called Prothymosin alpha, which is involved in various cellular processes and has multiple functions within the cell. Prothymosin alpha has been found to interact with High Mobility Group Box 1 (HMGB1), a DNA-binding protein involved in gene regulation, DNA repair, and inflammation [ 40 ]. This interaction is believed to be important for controlling mitochondrial oxidative phosphorylation, which is crucial for cellular energy production.…”

Single-cell transcriptomics reveals heterogeneity in esophageal squamous epithelial cells and constructs models for predicting patient prognosis and immunotherapy

“…Inhibition of PTMA expression was shown to substantially reduce the activity of ESCC cells while promoting apoptosis. Furthermore, PTMA was found to bind to HMGB1, influencing mitochondrial oxidative phosphorylation and impacting the malignant progression of ESCC ( 54 ). In our present study, we observed overexpression of the PTMA gene in esophageal cancer tissues, which was further validated through in vitro experiments.…”