Abstract
BackgroundKIF23 (kinesin family member 23) is a kinesin-like motor protein and plays an important role in cytokinesis. In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that KIF23 was upregulated in HCC tissues. At present, much less is known about its expression and functions in tumor cells. In this work, we aimed to investigate the expression of KIF23 in HCC and the correlation between its expression and clinical features.MethodsTotal RNA was extracted from 16 HCC and paired adjacent non-cancerous tissues. The expressions of the two KIF23 splice variants (KIF23 V1 and KIF23 V2) in normal and HCC tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Polyclonal antibody specific to KIF23 V1 was prepared, and the specificity of the antibody was confirmed by siRNA knockdown and Western blotting experiments. KIF23 protein expression in HCC was examined by immunohistochemistry staining with anti-KIF23 V1 or anti-KIF23 (commercially available for recognizing both KIF23 V1 and V2) antibodies, respectively. Univariate and Multivariate Cox regression analyses were used to determine the correlation between KIF23 protein expression and overall survival of HCC patients.ResultsThe two splicing variants of KIF23 mRNA were not detected in normal liver tissue by RT-PCR, but they were aberrantly expressed in HCC tissues. Immunohistochemistry staining with anti-KIF23 V1 antibody revealed that KIF23 V1 was mainly distributed in the nucleus, whereas the positive staining signals were predominantly in the cytoplasm when using anti-KIF23 antibody, suggesting that KIF23 V2 might localize in the cytoplasm of HCC cells. KIF23 V1 protein was detected in 57.6 % (83/144) HCC patients and the mean H-score was 42, while KIF23 V2 was detected in 94.4 % (135/143) HCC samples and the mean H-score was 68. Follow-up study showed that HCC patients with expression of KIF23 V1 had a longer 5-year survival (p = 0.0052), however, expression of KIF23 V2 protein did not associate with 3- and 5-year survival.ConclusionIn this study we show for the first time that KIF23 V1 and V2 have different localizations in HCC cells. Furthermore, KIF23 V1 protein expression might be a marker of longer overall survival in HCC patients.
Highlights
kinesin family member 23 (KIF23) is a kinesin-like motor protein and plays an important role in cytokinesis
Expressions of KIF23 V1 and V2 mRNA in normal and hepatocellular carcinoma (HCC) tissues To examine the distribution of mRNA expression of the two splice variants of KIF23, reverse transcriptase polymerase chain reaction (RT-PCR) was performed using cDNA reversed from mRNA of a variety of human tissues and human derived cancer cell lines
KIF23 V1 mRNA was detected in 81.2 % (13/16) of HCC tissues, while V2 mRNA was detected in 100 % (16/16) of HCC tissues
Summary
KIF23 (kinesin family member 23) is a kinesin-like motor protein and plays an important role in cytokinesis. In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that KIF23 was upregulated in HCC tissues. We have performed cDNA microarray analysis for mining differentially expressed genes in HCC in an attempt to identify new HCC biomarkers [5]. We found that the expression of KIF23 showed a 6-fold increase in HCC tissues compared with paired non-cancerous tissues. To date, only few studies have been reported on the expressions of KIF23 in tumor cells. Valk K et al found that KIF23 is upregulated in non-small cell lung cancer (NSCLC) in screening differentially expressed genes in NSCLC [14]. Takahashi S et al reported a higher level of KIF23 expression in glioma tissues compared to normal brain tissue [15]. The expression of KIF23 in HCC tissues remains unknown
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