NIMA-Related Kinase 6 as an Effective Target Inhibits the Hepatocarcinogenesis and Progression of Hepatocellular Carcinoma

BackgroundNever in Mitosis Gene A-Related Kinase (NEK), a member of the cell cycle-dependent protein kinase, encodes a serine/threonine protein kinase involved in mitosis of the G2-M transition period. Eleven NEKs have been identified, and NEK6 is one of them. It has been confirmed that NEK6 is over-expressed in some tumor cell lines. The following study aims to explore the expression of NEK6 in hepatocellular carcinoma (HCC) and the correlation between NEK6 expression and clinical features.MethodsLiver tissues of 79 HCC patients and other patients were obtained during various liver surgeries. Total RNA from these tissue samples was extracted and QPCR was adopted to detect positive expression of NEK6. The correlation between NEK6 expression and the clinical characteristics of HCC was analyzed. The expression of NEK6 in different cell lines (LO-2, HepG2, Li-7, Huh-7, and BEL-7402) was quantified via QPCR. Scratch assay, Transwell assay, and tumor-formation assay in nude mice were used to evaluate the effects of NEK6 on the HCC progression in vitro and in vivo.ResultThe expression of NEK6 was up-regulated in HCC tissue compared with other tissues. The proportion of hepatitis B virus infection in the Nek6 Overexpression group was higher than the Control group (P=0.045). The multiple tumors and bigger tumors (>5 cm) seemed more common in the NEK6 overexpression group (P=0.018, and P=0.037, respectively). Further analysis showed that the overexpression of NEK6 was correlated with hepatitis B virus infection and tumor diameter (P=0.045; P=0.038). The 3-year disease-free survival (DFS) and overall survival (OS) of patients in the NEK6 overexpression group were 14.1% and 33.4%, which were worse than the control group. Tumor size over 5 cm and portal vein invasion were risk factors for both DFS and OS. Nek6 overexpression did not seem to affect the prognosis as a risk factor. Among the human cell lines, the expression of NEK6 was higher in Li-7 cells and HepG2 cells. The migration and invasion capabilities of Li-7 and HepG2 cells were suppressed when the NEK6 expression was down-regulated. The xenograft tumor weight was significantly lighter in the shNEK6 group (P < 0.05). ConclusionThe results from the study demonstrated that the expression level of NEK6 was up-regulated in HCC and correlated with the HCC progression, suggesting it might be a clinically valuable biomarker and serve as a potential therapeutic target for treating HCC.