USP21 accelerates the proliferation and glycolysis of esophageal cancer cells by regulating the STAT3/FOXO1 pathway

Esophageal cancer (EC) is one of the malignant tumors with high morbidity and mortality in digestive system all over the world. USP21 has been discovered to be dys-expressed to exhibit vital roles in multifarious cancers. However, its role and molecular mechanisms in EC are not elucidated. In this work, it was demonstrated that USP21 expression was up-regulated in ECSA tissues through UALCAN and TIMER databases. Additionally, through IHC assay and western blot, it was further identified that USP21 exhibited higher expression in EC tissues and cells. Further investigations illustrated that USP21 facilitated cell proliferation and glycolysis in EC. Next, the influences of USP21 on the STAT3/FOXO1 pathway in EC were investigated. We discovered that USP21 modulated the STAT3/FOXO1 pathway, and the decreased cell proliferation and glycolysis mediated by USP21 knockdown could be rescued by FOXO1 inhibition. At last, USP21 aggravated tumor growth in vivo. In conclusion, our work was the first time to probe the potential function and regulatory mechanism of USP21 in EC, and these above findings manifested that USP21 accelerated the proliferation and glycolysis of EC cells through regulating the STAT3/FOXO1 pathway. This discovery implied that USP21 may be a promising prognostic and therapeutic biomarker for EC patients.