Ubiquitin Conjugating Enzyme E2 C (UBE2C) has a key oncogenic role in many human malignancies, including gastric cancer. However, it remains largely unknow at which level UBE2C expression is altered, as well as what are the downstream targets of UBE2C. In this study, we show that UBE2C is frequently overexpressed in gastric cancer patients. Interestingly, high expression of UBE2C mRNA instead of genome amplification is the predominant alterations observed in both stomach adenocarcinoma. We then confirmed that silencing UBE2C not only suppresses gastric cancer colony formation, but also inhibits DNA biosynthesis. Furthermore, we discovered that microRNA-300 is able to suppress gastric cancer progression through reducing UBE2C mRNA abundance, which is protected by an RNA binding protein HuR. Lastly, through an analysis of genes whose expressions correlate with that of UBE2C from gastric cancer cell lines, we have proposed several key genes that can be regulated by UBE2C, contributing to its oncogenic activity. (C) 2020 Elsevier Inc. All rights reserved.