Downregulation of PHLDA2 promotes apoptosis and autophagy in endometrial cancer cells while inhibiting their proliferation and metastasis

Background: Pleckstrin homology-like domain family A member 2 (PHLDA2) has been implicated as a potential inhibitor of apoptosis and may contribute to tumorigenesis. Here, we report on the function of PHLDA2 in endometrial cancer (EC). Methods: Small interfering RNA (siRNA) was utilized to reduce PHLDA2 expression in EC cells. Subsequently, cell proliferation, apoptosis, migration and invasion abilities were evaluated. Autophagy was examined through Microtubule-associated protein 1 light chain 3 beta (LC3B) immunofluorescence staining. Protein expression levels were determined by Western blotting. Results: PHLDA2 expression was significantly elevated in EC cell lines, and its knockdown was found to reduce cell proliferation, migration, and invasion while enhancing apoptosis. Moreover, induction of autophagy was observed with PHLDA2 knockdown, marked by elevated LC3B conversion and diminished P62 expression. Additionally, the fall in phosphorylation levels of Phosphatidylinositol 3-kinase (PI3K), Protein kinase B (AKT) and Glycogen synthase kinase-3 beta (GSK-3β) was examined following PHLDA2 knockdown. Conclusions: PHLDA2 knockdown can impede the malignant progression of EC cells by promoting apoptosis and autophagy, potentially through inactivation of the PI3K/AKT/GSK-3β pathway.