Abstract
BackgroundHepatocellular carcinoma (HCC) still remains a dominating medical challenge in early diagnosis and clinical therapy. Centromere protein M (CENPM) has been proved to be over-expressed in HCC tissues, but carcinogenic mechanism of CENPM contributing to liver cancer is poorly understood.MethodsIn this study, we first explored mRNA and protein levels of CENPM in HCC samples, matching adjacent non-tumor tissues and six hepatoma cell lines by polymerase chain reaction (PCR), western blotting and immunohistochemistry (IHC). Clinical data of HCC patients downloaded from The Cancer Genome Atlas (TCGA) were also analyzed. The character of CENPM concerned with HCC progression through several functional experimentations in vitro and in vivo was researched. Bioinformatics was carried out to further discover biological functions of CENPM.ResultsCENPM was positively up-regulated in HCC and connected with a poor prognosis. Silencing CENPM repressed cell proliferation in vivo and in vitro, and knock-down CENPM inhibited cell migration and invasion. Additionally, depletion of CENPM can promote cell apoptosis and arrested cell cycle. Furthermore, single-gene gene set enrichment analysis (GSEA) analysis indicated that CENPM was linked to the P53 signaling pathway and cell cycle pathway, and our research supported this prediction. Finally, we also found that miR-1270 was a negative regulator and participated in post-transcriptional regulation of CENPM, and hepatitis B virus X protein (HBx) can promote hepatocellular carcinoma by suppressing miR1270.ConclusionCENPM was closely associated with HCC progression and it could be considered as a new possible biomarker along with a therapeutic target for HCC.
Highlights
Hepatocellular carcinoma (HCC) still remains a dominating medical challenge in early diagnosis and clinical therapy
The expression of Centromere protein M (CENPM) in different gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets We first checked the mRNA level of CENPM in 24 kinds of tumor types from TCGA to figure out the CENPM whether was a oncogene or a tumor suppressor, and found that the expression of CENPM was almost higher in tumor group than corresponding normal group (Fig. 1a)
CENPM was remarkly over-expressed in HCC and associated with poor prognosis As mentioned previously, the expression of CENPM from GEO database was significantly up-regulated in tumor group compared with normal group (Fig. 2a-b)
Summary
Hepatocellular carcinoma (HCC) still remains a dominating medical challenge in early diagnosis and clinical therapy. Centromere protein M (CENPM), referred as proliferation associated nuclear element 1 (PANE1), is a kind of kinetochores protein which was detected in mouse mammary epithelium [12] and participated in affecting chromosome separation in the progress of cellular division [13]. CENPM was kinetochores protein that associated with microtubules to regulate chromosome segregation during cell division, and took part in the biological function of the cell cycle [14, 15]. The expression of CENPM and centromere assembly should be controlled closely during the cell cycle, and mistakes in this regulation may result in aneuploidy. Numerous researches pointed out some genes, including CENPA [17], CENPE [18], and CENPF [19, 20], which were homogeneous and closely correlated with tumors, and the results manifested that highexpression of centromere protein family could have a significant impact on the proliferation and invasion of tumors
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