Paeonol inhibits the progression of endometrial cancer by affecting TRIM26-mediated LDHA ubiquitination modification.

Endometrial cancer (EC) is a common gynecological malignancy characterized by abnormal glucose metabolism. Paeonol (Pae), a natural phenolic compound derived from traditional Chinese medicine, exhibits broad-spectrum antitumor activity. However, its role in modulating glycolysis and the underlying molecular mechanisms in EC remain poorly understood. The effects on EC cell viability (CCK-8), proliferation (EdU), apoptosis (flow cytometry), invasion (transwell), migration (wound healing), and tube formation rate were assessed. Glycolytic parameters were measured using corresponding commercial kits. Protein and mRNA expression levels were determined by Western blotting and RT-qPCR. The interaction between tripartite motif protein 26 (TRIM26) and lactate dehydrogenase A (LDHA) was investigated through co-immunoprecipitation (Co-IP), cycloheximide (CHX) chase, and ubiquitination assays. A xenograft model was established to examine the in vivo efficacy of Pae. Pae inhibited proliferation, metastasis, tube formation, and glycolysis of EC cells, and induced apoptosis. Pae suppressed EC malignant behaviors by downregulating LDHA expression. TRIM26 promoted ubiquitination-mediated degradation of LDHA. Overexpression of LDHA reversed the tumor-suppressive effects of TRIM26 overexpression in EC cells. TRIM26 knockdown attenuated the antitumor effects of Pae. In vivo experiments demonstrated that Pae inhibited tumor growth and regulated TRIM26/LDHA expression. Pae was found to promote TRIM26 expression, which in turn enhanced TRIM26-mediated ubiquitination and degradation of LDHA, thereby contributing to glycolysis inhibition and suppression of EC progression. These results suggested that Pae might exert its effects by modulating the TRIM26/LDHA axis and supported its potential therapeutic value in EC.