USP5 Promotes Uterine Corpus Endometrial Carcinoma Cell Growth and Migration via mTOR/4EBP1 Activation
Yinghua Li, Jian Zhou
Abstract
BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) is a common malignancy worldwide developed in the female reproductive system, which can be life-threatening due to metastasis and poor prognosis. Deubiquitinating enzymes (DUBs) play key roles in ubiquitin-proteasome system. As a member of DUBs, the ubiquitin-specific protease 5 (USP5) has been found to be an oncogene in several cancers. This study aims to explore the function of USP5 in UCEC. MATERIALS AND METHODS: Clinical significance of USP5 was assessed from The Cancer Genome Atlas (TCGA) UCEC dataset. Knockdown and overexpression were performed by transfecting the cells with siRNAs and pCDNA3.1 vectors, respectively. CCK8, colony formation, wound healing, transwell, PI, and PI/annexin V staining were conducted to check the effect of USP5 on cellular biology function. Western blot assay was used to detect protein expression. RESULTS: USP5 was upregulated in UCEC patients. Its downregulation led to decreased migration and proliferation of UCEC cells, and meanwhile, cell cycle arrest and apoptosis were induced. By contrast, USP5 overexpression significantly promoted cell migration and cell mitosis. Further study revealed that USP5 could cause hyperactivation of mTOR/4EBP1 pathway and rapamycin treatment could totally reverse the effects of UPS5 overexpression. CONCLUSION: Our data demonstrated that USP5 functioned as an oncogene in UCEC, which provided new insights into the pathogenesis of UCEC and a promising molecular target for UCEC diagnosis and therapy.