Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the third most frequent cause of cancer-related death worldwide[1]
KIF4A expression increases in HCC tissues and cell lines To assess the role of KIF4A in HCC, we analysed four microarray datasets from Oncomine database, and found significant overexpression of KIF4A in the majority of HCC tissues compared with adjacent non-neoplastic controls (Supplementary Fig. S1)
HCC is characterized by multiple cancer hallmarks, including genetic and epigenetic alterations that cause uncontrolled cellular proliferation and cell cycle regulation
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the third most frequent cause of cancer-related death worldwide[1]. Despite great advances having been made to increase significantly the detection rate in early stages of HCC patients, the 5-year overall survival rate of patients with liver cancer, in intermediate stage and advanced stage, is still extremely low[2]. A growing body of related research was performed in order to explain the oncogenesis process of HCC, the molecular basis still remains obscure. Revealing the complicated molecular mechanism of pathogenesis and development of liver cancer is currently an urgent global health issue. There has been an improvement in the classification of the molecular pathogenesis of HCC3. Common mutations affect telomere maintenance (telomere reverse transcriptase (TERT)), WNT pathway
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