Upregulate KIF4A Enhances Proliferation, Invasion of Hepatocellular Carcinoma and Indicates poor prognosis Across Human Cancer Types

Abstract

Hepatocellular carcinoma (HCC) is one of the most aggressive and heterogeneous cancers worldwide. Herein, we demonstrate KIF4A (Chromosome-associated kinesin KIF4A) as a potential biomarker, is up-regulated in most samples of HCC. The expression level of KIF4A in tumor tissue is significantly associated with the survival time, and a significant correlation between KIF4A expression and clinical information stage, metastasis and tumor dimension was observed. We further measured the proliferation and migration ability of two HCC cell lines, HCC-LM3 and PLC/PRF/5, following KIF4A-siRNA transfection. Knocking down of KIF4A significantly reduced migration and proliferation ability. Moreover, we also measured the proliferation and migration ability of two HCC cell lines through KIF4A overexpression, and found that KIF4A overexpression could enhance migration and proliferation ability, indicating that KIF4A exhibits oncogenic effects. Besides, study based on TCGA cohorts also reveals high KIF4A mRNA expression are significantly associated with shorter overall survival in multiple cancer types. Gene sets enrichment analysis exhibited that cell cycle related pathways and p53 signaling pathways to be top altered pathways of in KIF4A-high expression group in HCC, suggesting the potential role of KIF4A in mediating tumor initiation and progression. In summary, our work identified KIF4A as a potential predictive and prognostic marker for hepatocellular carcinoma.

Identification of Crucial Genes Associated With Immune Cell Infiltration in Hepatocellular Carcinoma by Weighted Gene Co-expression Network Analysis

“…CENPA expression was reported to be significantly elevated in HCC tissues compared with normal tissues in TCGA and GEO, and the overexpression of CENPA was closely associated with HBV x gene (HBx) COOH mutation in HCC (Liu et al, 2012;Long et al, 2018). Gene concentration analysis revealed the pathway related to cell cycle and the p53 signal pathways as the most important pathways in the high-expression group of KIF4A in HCC, indicating that KIF4A plays a potential role in mediating the occurrence and development of tumors (Hou et al, 2017). DTYMK is a novel gene associated with mitochondrial DNA depletion syndrome (Lam et al, 2019) and prognosis of HCC (Yeh et al, 2017).…”

Increased KIF4A expression is a potential prognostic factor in prostate cancer

“…In addition, Hou et al demonstrated that KIF4A was overexpressed in hepatocellular carcinoma (HCC) tissue, which was significantly associated with survival time and clinical information (stage, metastasis and tumor dimension). Further functional analysis of siRNA-mediated silencing and KEGG pathway enrichment analysis showed that KIF4A promoted HCC cell growth and metastasis by mediating cell cycle-related and p53 signaling pathways ( 20 ). In the present study, using DGEA we found that KIF4A was highly expressed in CRPC, and further survival analysis showed that KIF4A may be an important oncogene.…”

“…Furthermore, KIF4A overexpression enhanced migration and proliferation in lung cancer and HCC ( 18 , 20 ), and KIF4A was found to control cellular proliferation via spindle assembly checkpoint (SAC) activation ( 17 – 20 ). Recent studies have revealed that the KIF4 subfamily is important in tumor development and progression ( 9 – 14 ).…”

KIF4A facilitates cell proliferation via induction of p21-mediated cell cycle progression and promotes metastasis in colorectal cancer

“…Notably, cells affected by aneuploidy are characterized by the loss of genetic stability, which is intensely suspected to be associated with tumorigenesis 13 . Previous studies have also demonstrated that KIF4A functions as an oncogene and plays critical roles in several malignancies, such as lung cancer, oral cancer 14 , breast cancer 15 , cervical carcinoma 16 , and hepatocellular carcinoma 17 . Nevertheless, the expression profile and the function of KIF4A in CRC remain unknown.…”