Abstract
NIMA-related kinase-7 (Nek7) is a serine/threonine kinase involved in cell-cycle progression via mitotic spindle formation and cytokinesis. In this study, we investigated whether Nek7 involves in hepatocellular carcinoma (HCC). Interestingly, we found that Nek7 was significantly overexpressed in HCC than in liver tissues. In HCC patients, high Nek7 expression was significantly correlated with tumor numbers, tumor diameter, adjacent organs invasion, tumor grade and TNM stage. Furthermore, Nek7 expression pattern showed close relationship with that of Ki-67, a well-stablished cell proliferation marker. More importantly, patients with higher expression levels of Nek7 had significantly lower 5-years survival rate. Likewise, Nek7 expression was significantly higher in HCC cell lines than normal hepatic cell line. By Nek7 silencing using lentivirus-mediated Nek7 interference approach, the growth of HCC cell lines was inhibited and the tumor growth in xenograft mouse model was also suppressed. Mechanistic studies showed that silencing of Nek7 resulted in decreasing cyclinB1 level both in vitro and in vivo. In conclusion, this study highlights for the first time the possible role of Nek7 in HCC progression. Nek7 would be a useful biomarker that early predicts HCC patients at higher risk of poor prognosis. Also, Nek7 could be a novel HCC therapeutic target.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor, and the second most common cause of cancer deaths worldwide [1,2]
We found a close relationship between NIMA-related kinase-7 (Nek7) and Ki-67 indicating that Nek7 might play an important role in HCC cell proliferation
HCC cell lines (HepG2, HuH7, Hep3B and SMMC7721) than in the normal hepatic cell line; LO2 (Figure 1B). To further confirm this finding, the mRNA level of Nek7 was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis in 80 HCC tissues and their matched non-cancerous liver tissues
Summary
Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor, and the second most common cause of cancer deaths worldwide [1,2]. Identification of target molecules and molecular mechanisms underlying the development and progression of HCC are of particular importance. In this context, The Nek (NIMA Related Kinase) protein kinase family includes 11 members which were originally identified as human orthologs to the Aspergillus nidulans protein kinase, NIMA (Never In Mitosis, gene A) kinase [5,6]. Nek is highly expressed in gallbladder cancer compared to normal tissues, and has significant relationship with tumor differentiation, metastasis and patients survival rate [12]. Ki-67 is a well-established biomarker for www.impactjournals.com/oncotarget cell proliferation and its biological role in the HCC progression has been suggested. Ki-67 is a well-established biomarker for www.impactjournals.com/oncotarget cell proliferation and its biological role in the HCC progression has been suggested. [14,15,16,17,18]
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