Abstract
Never in mitosis gene A-related kinase (Nek) 6 is a recently identified Nek that is required for mitotic cell cycle progression; however, the role and mechanism of Nek6 activity during hepatocarcinogenesis is not well known. The aim of this study was to investigate the potential roles and internal mechanism of Nek6 in hepatocellular carcinoma (HCC) development. In the present study, Nek6 was found to be overexpressed in HCC samples and cell lines by florescent real-time quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. Furthermore, it was evidenced to contribute to oncogenesis and progression. The ectopic overexpression of Nek6 promoted cell proliferation and colony formation, whereas gene silencing of Nek6 inhibited these phenotypes, as documented in Huh7, PLC/PRF/5, Hep3B and HepG2 HCC cell lines. Mechanistic analyses indicated that Nek6 regulates the transcription of cyclin B through cdc2 activation, and promotes the accumulation of G0/G1-phase cells. In conclusion, the findings of the current study suggested that Nek6 contributes to the oncogenic potential of HCC, and may present as a potential therapeutic target in this disease.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common types of malignancy globally, with >600,000 mortalities perKey words: never in mitosis gene A‐related kinase 6, proliferation, cyclin B, hepatocellular carcinoma, cdc2 year, and its incidence continues to increase [1]
Nek6 was found to be significantly upregulated in 38 (79.1%) of the 48 HCC speci‐ mens, whereas the transcript of the gene was rarely detected in adjacent non‐cancerous livers, using a semi‐quantitative reverse transcription (RT)‐PCR assay (Fig. 1A)
The results showed that the protein levels of Nek6 were increased in HCC when compared with the adjacent non‐cancerous livers (Fig. 1B)
Summary
Hepatocellular carcinoma (HCC) is one of the most common types of malignancy globally, with >600,000 mortalities per. Cell cycle deregulation is one of the hallmarks in human cancer and, identification of physiological targets under‐ lying regulatory mechanisms for cell cycle regulation is critical in the development of novel and effective cancer therapies [4,5,6]. Studies have identified that members of the never in mitosis gene A‐related kinase (Nek) family are involved in cell cycle progression [7,8,9]. Neks are essential for mitotic entry, possibly through regulation of the cdc2‐cyclin B axis [10]. As a member of the Nek family, Nek appears to be involved in cancer. It has been shown that the Nek transcript is significantly upregulated in a series of solid tumors, including HCC [11,12]. The precise molecular mechanism whereby Nek contributes to HCC remains unclear
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