Upregulation of kinesin family member 4A enhanced cell proliferation via activation of Akt signaling and predicted a poor prognosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death worldwide, and the molecular pathogenesis and development of HCC are largely unknown. In the present study, we found that KIF4A expression was upregulated in HCC (678 samples, P = 2.03E-8) based on a meta-analysis of Oncomine database. We further confirmed that both KIF4A mRNA and protein expressions were overexpressed in human HCC tumour tissues as well as cancer cell lines. Higher KIF4A expression was correlated with poorer overall survival (P < 0.0001) and disease-free survival (P < 0.0337) in HCC patients. We constructed in vitro KIF4A overexpression and depletion HCC cell models. KIF4A overexpression significantly enhanced cellular proliferation and clonogenic abilities, whereas KIF4A depletion caused a dramatic increase of cells with abnormal chromosome segregation and subsequently resulted in augmentation of apoptosis in HCC cells. In addition, we demonstrated that KIF4A depletion was related to inhibition of Akt kinase activity and induction of intrinsic apoptosis signaling pathway. Taken together, KIF4A may act as a prognostic biomarker and potential therapeutic target in human HCC.