NEK6 Accelerates Hepatocellular Carcinoma Progression and Glycolysis through Ubiquitination of TCP10L.

Abstract

Never in mitosis a related kinases 6 (NEK6) is a serine/threonine kinase, and dysregulation of NEK6 is associated with malignant progression of human cancers. Nonetheless, the biological function and molecular mechanism of NEK6 in hepatocellular carcinoma (HCC) are unknown. Our study found that NEK6 was obviously raised in HCC patient tissues and cells, and patients with high NEK6 expression had a worse prognosis. Silencing of NEK6 reduced the growth, metastasis, cell cycle, and glycolysis of HCC cells while facilitating apoptosis. In vivo experiments also showed that NEK6 knockdown dramatically hampered tumor growth, suggesting that NEK6 enhanced HCC progression in vivo and in vitro. Next, we proved that TCP10L was a target gene of NEK6, and NEK6 negatively regulated TCP10L expression. Mechanistically, we confirmed that NEK6 was bound to TCP10L, and NEK6 degraded TCP10L protein expression through ubiquitination. Rescue experiments also declared that TCP10L reversed the effect of NEK6 on HCC cells. Our results disclosed that NEK6 heightened HCC progression and glycolysis through ubiquitination of TCP10L. Our study may provide a new perspective for the treatment of HCC.