Li Qiuhong, Zhong Jie, Yang Shangjie, Liang Yanping
Department of Obstetrics and Gynecology, Shanghai Yangpu District Shidong Hospital, Shanghai 2000438, P.R. China.
Department of Obstetrics and Gynecology, Yangpu Hospital Affiliated to Tongji University, Shanghai 200090, P.R. China.
Oncol Lett. 2022 Mar;23(3):98. doi: 10.3892/ol.2022.13218. Epub 2022 Jan 27.
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.
子宫内膜癌（EC）具有极其恶性的生物学行为，死亡率很高。近年来，EC已成为全球女性中最致命的癌症之一。E3泛素连接酶在健康细胞的生物学功能中起重要作用，但也可能促进肿瘤发生和癌症发展。含PDZ结构域的环指蛋白3（PDZRN3）与细胞分化相关，其结构包括E3泛素连接酶。然而，PDZRN3在EC中的作用仍不清楚。采用逆转录定量PCR检测EC细胞中PDZRN3的表达水平，并通过蛋白质印迹法、MTT法、集落形成实验、Transwell实验、皮下肿瘤形成实验和肺转移实验确定PDZRN3在EC进展中的作用。进行多通路报告基因阵列和蛋白质印迹法以研究PDZRN3在EC中的潜在生物学机制。本研究表明，PDZRN3在EC的转移和增殖中起重要作用。与正常子宫内膜组织相比，EC组织中PDZRN3的表达较低。EC中PDZRN3的低表达水平与EC患者的某些临床病理特征相关，如患者年龄、肿瘤分级和肿瘤亚型。体内和体外实验证实，PDZRN3低表达的EC细胞的侵袭和增殖活性比PDZRN3高表达的EC细胞更强。此外，PDZRN3的低表达通过激活经典Wnt信号通路促进转移和增殖。本研究表明，PDZRN3表达降低通过激活经典Wnt信号通路促进EC细胞的转移和增殖，突出了EC治疗的潜在生物学靶点。
