NUCKS1 exacerbates hepatocellular carcinoma cell proliferation and metastasis via the upregulation of Cdc42.

Nuclear casein kinase and cyclin-dependent kinases substrate 1 (NUCKS1) is overexpressed in hepatocellular carcinoma (HCC), but its role and regulatory mechanism in the development and progression of HCC remains unknown. Here, we report that the RNA and protein levels of NUCKS1 were significantly increased in HCC tissues. The inhibition of NUCKS1 notably decreased the proliferation and migration of SNU449 and HepG2 cells. However, NUCKS1 overexpression exacerbated cell growth and migration. Additionally, NUCKS1 depletion reduced the sphere formation efficiency and inhibited tumorigenesis in vivo. Mechanistically, depletion of NUCKS1 downregulated the expression of cell division control protein 42 (Cdc42), and NUCKS1 directly bound to the promoter of Cdc42 and transcriptionally upregulated Cdc42, which promoted the development and progression of HCC. Furthermore, the expression of NUCKS1 was positively associated with Cdc42 in HCC tissues. Collectively, our data indicate that the increasing expression of NUCKS1 plays an oncogenic role and promotes progression via transactivation of Cdc42 expression in HCC.