Abstract
To investigate the mechanism of kinetochore-associated protein 1 (KNTC1) in hepatocellular carcinoma. To query the TCGA database for KNTC1 expression in hepatocellular carcinoma. Detection of protein and mRNA levels of KNTC1 in hepatocellular carcinoma cell lines SK-Hep-1, Huh7, HepG2 and SNU449. Cell proliferation, migration and invasion ability were examined after KNTC1 knockdown in SK-Hep-1 and Huh7. Proteins related to KNTC1 were identified through protein interregulation, and their role in hepatocellular carcinoma was investigated. Our results showed that KNTC1 was significantly upregulated in hepatocellular carcinoma tissues and was associated with poorer prognostic survival. The expression of KNTC1 in hepatocellular carcinoma cell lines SK-Hep-1, Huh7, HepG2 and SNU449 was significantly higher than that in normal hepatocyte line L02. Knockdown of KNTC1 in SK-Hep-1 and Huh7 significantly inhibited cell viability, migration ability and invasion ability. KNTC1 is involved in the regulation of hepatocellular carcinoma through its interaction with cyclin-dependent kinase 1 (CDK1). Knockdown of KNTC1 inhibited CDK1 expression, while CDK1 overexpression was able to rescue the regulation of KNTC1 on the viability, migration and invasive ability of hepatocellular carcinoma cell lines. Knockdown of KNTC1 was found to resulted a cell cycle arrest at the S-phase, potentially through the modulation of CDK1, leading to decreased migration and invasion of hepatocellular carcinoma cells. Moreover, knockdown of KNTC1 in mouse transplanted tumors significantly inhibits tumor growth. Inhibition of high expression of KNTC1 in hepatocellular carcinoma was effective in suppressing the progression of hepatocellular carcinoma cells after knockdown. It may be a potential target for the treatment of hepatocellular carcinoma.