Cyclin B2 Overexpression in Human Hepatocellular Carcinoma is Associated with Poor Prognosis

Abstract

Background and aims: Cyclin B2 (CCNB2) has been reported to be highly expressed in a few malignancies. However, the biological function of CCNB2 in hepatocellular carcinoma (HCC) is largely unknown. We aimed to investigate the effect of CCNB2 in HCC.

Methods: The expression of CCNB2 in HCC and normal liver tissues and connection of its expression with prognosis and clinical parameters were studied. The effect of knocking down CCNB2 on cell proliferation, migration, cell cycle distribution, and apoptosis were estimated in BEL-7404 cells.

Results: Compared to normal liver tissues, the level of CCNB2 was higher in HCC tissues from the Gene Expression Profiling Interactive Analysis (GEPIA). The 5 year overall survival and disease-free survival of HCC patients with high CCNB2 levels were shorter than that of those with low CCNB2 levels. Immunohistochemistry analysis also discovered the expression differences of CCNB2 in HCC and normal liver tissues and showed that CCNB2 expression was significantly associated with tumor number, tumor size, tumor thrombus, and alanine aminotransferase level. CCNB2 expression was higher in HCC cell lines (BEL-7404, Hep3B, BEL-7402, and SMMC-7721) than that in the normal hepatic cell line (HL-7702). Knockdown of CCNB2 inhibited cell proliferation and migration, promoted cell apoptosis, and caused S phase arrest in BEL-7404 cells. Finally, CCNB2 was associated with Polo Like Kinase 1 (PLK1) in the GEPIA database and BEL-7404 cells.

Conclusions: CCNB2 may serve as a prognostic factor and participated in the development and progression and promote cell proliferation and migration through CCNB2/PLK1 pathway in HCC.

Keywords: Cyclin B2; Hepatocellular carcinoma; Migration; Prognosis; Proliferation.