The role of Nek2 in hepatocellular carcinoma

Abstract

Liver cancer is one of the most prevalent cancers over the world and particularly affects people in some East Asia countries such as Korea, Japan and China. In Hong Kong, liver cancer is the third killer among different types of cancer. The NIMA-related kinase 2 (Nek2), which regulates centrosome separation, is a potential player in carcinogenesis. Our evidence showed that the mRNA and protein levels of Nek2 are up-regulated in liver cancer cells. Since Nek2 is pertinent to centrosome cohesion, we speculate that it might take part in carcinogenesis through centrosome regulation. To study the effect of Nek2 in chromosomal instability, centrosome splitting and cell cycle, a stable isoform Nek2A overexpression inducible system was generated in different hepatocellular carcinoma (HCC) and bone osteosarcoma cell lines for investigations through immunofluorescence staining and flow cytometry analysis. In both Nek2A inducible HepG2 and SMMC-7721 cells, a higher proportion of cells with centrosome splitting was observed in the Nek2A overexpressing cells. However, in Nek2A inducible U2OS cells, where p53 was suppressed, induced expression of Nek2A led to a significant increase in cells with multiple centrosomes. Moreover, cell cycle analysis showed an increased content of DNA when Nek2A is overexpressed, suggesting that Nek2A induces more aneuploid cells. To conclude, overexpression of Nek2 exacerbates chromosomal instability. Dysregulation of centrosome may be the key for understanding of regulatory mechanism of chromosomal instability by Nek2.