UBE2K promotes the malignant progression of hepatocellular carcinoma by regulating c-Myc.

ABSTRACT

Hepatocellular carcinoma (HCC) is a serious threat to human health and life due to its high morbidity and mortality. Ubiquitin-conjugating enzymes are players in the ubiquitin proteasome system and are responsible for a great number of physiological activities in cells. The action of ubiquitin-conjugating enzyme UBE2K in HCC has not been reported. Therefore, we studied the function and role of UBE2K in the malignant progression of HCC. An analysis of UBE2K expression in HCC cells was performed using RT-qPCR and protein immunoblotting. CCK-8, Transwell and sphere formation assays were used to identify the potential effects of UBE2K in HCC cell proliferation, migration and stemness property. RT-qPCR, and protein immunoblotting experiments was taken to explore the regulation between UBE2K and c-Myc. Here, we discovered that UBE2K expression was elevated in HCC cells, and elevated UBE2K predicts worse prognosis for HCC patients. Functionally, UBE2K promote, while UBE2K knockdown suppressed cell proliferation, migration and stemness property of HCC cells. Furthermore, c-Myc was identified as a downstream target of UBE2K. Moreover, functional rescue experiments finally proved that UBE2K facilitates the malignant progression of HCC cells by upregulating c-Myc. We clarified through in vivo experiments that UBE2K expression promotes tumor growth in HCC. Taken together, our study results proved the molecular regulation of UBE2K and c-Myc in HCC and the oncogenic role of UBE2K/c-Myc axis in HCC progression, thus it provides a promising molecular target for the diagnosis and treatment of HCC.