Abstract
Ubiquitin-specific protease 14 (USP14), a member of the USP family, which catalyzes ubiquitin cleavage from a range of protein substrates, has been found dysregulated in several cancers. Our aim is to explore the functions and mechanism of USP14 in endometrial carcinoma (EC). Quantitative real-time PCR (qRT-PCR) and western blot (WB) were used to assess USP14 levels in EC tissues and adjacent nontumor tissues. USP14 overexpression or knockdown models were adopted to determine USP14-mediated effects on EC cell proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). The xenograft tumor experiment checked the effect of USP14 overexpression on tumor cell growth. Furthermore, the upstream signaling pathway of USP14 was predicted by bioinformatics. Consequently, EC tissues exhibited USP14 overexpression compared to normal paracancerous nontumor tissues. USP14 presence was linked to an adverse prognosis in EC cases. Functionally, USP14 overexpression reduced apoptosis and increased cell migration, invasion, and EMT in vivo and ex vivo. USP14 knockdown had the opposite effect. Mechanistically, NF-κB pathway activation occurred through the inhibitory effect of USP14 on I-κB expression. Conversely, NF-κB pathway inhibition attenuated USP14-mediated carcinogenic effects. Additionally, there existed a binding interaction between miR-124-3p and the 3'-UTR of USP14, resulting in USP14 activity inhibition. In summary, our research indicates that the involvement of miR-124-3p in USP14 regulation contributes to exacerbated EC progression through NF-κB pathway activation. The modulation of this pathway may be a new strategy for treating EC.