Lower expression of PDZRN3 induces endometrial carcinoma progression via the activation of canonical Wnt signaling

Abstract

Endometrial carcinoma (EC) exhibits an extremely malignant biological behavior and has a high mortality rate. EC has recently become one of the most lethal cancers in women worldwide. E3 ubiquitin ligases play an important role in the biological function of healthy cells but can also contribute to tumorigenesis and cancer development. PDZ Domain Containing Ring Finger 3 (PDZRN3) is associated with cell differentiation and its structure includes the E3 ubiquitin ligase. However, the effects of PDZRN3 in EC remain unclear. Reverse transcription-quantitative PCR was used to detect the expression levels of PDZRN3 in EC cells, and the role of PDZRN3 in EC progression was determined using western blotting, MTT, colony formation, Transwell, subcutaneous tumor formation and pulmonary metastasis assays. A multi-pathway reporter arrays and western blotting were performed to investigate the potential biological mechanisms of PDZRN3 in EC. The present study demonstrated that PDZRN3 served an essential role in metastasis and proliferation of EC. PDZRN3 expression was lower in EC tissues compared with that in normal endometrial tissues. Low expression level of PDZRN3 in EC was correlated with certain clinicopathological features of patients with EC, such as the age of the patients, the tumor grade and the tumor subtype. The invasive and proliferative activities of EC cells with low expression of PDZRN3 were more potent than those of EC cells with high expression of PDZRN3, which was confirmed by in vivo and in vitro experiments. Furthermore, lower expression of PDZRN3 promoted metastasis and proliferation via activation of the canonical Wnt signaling pathway. The present study demonstrated that decreased PDZRN3 expression promoted metastasis and proliferation in EC cells via activation of the canonical Wnt signaling pathway, highlighting a potential biological therapeutic target for the management of EC.