Abstract
Aberrant chromobox (CBX) family protein expression has been reported in a variety of human malignancies. However, the role of CBX6 in hepatocellular carcinoma (HCC) progression and patient prognosis remains unknown. In this study, we found that CBX6 was frequently up-regulated in HCC clinical samples and HCC cell lines and that CBX6 expression was significantly correlated with larger tumor sizes (≥ 5 cm, p = 0.011) and multiple tumors (n ≥ 2, p = 0.018). Survival analyses indicated that patients with higher CBX6 expression levels had significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with lower CBX6 expression levels, and multivariate analyses confirmed that increased CBX6 expression was an independent unfavorable prognostic factor for HCC patients. Functional study demonstrated that CBX6 profoundly promoted HCC cell growth both in vitro and in vivo, and mechanistic investigation revealed that the S100A9/NF-κB/MAPK pathway was essential for mediating CBX6 function. In conclusion, our results represent the first evidence that CBX6 contributes to tumor progression and indicate that the protein may serve as a novel prognostic biomarker for HCC and as a therapeutic target in the treatment of the disease.
Highlights
Primary liver cancer is the fifth-most common cancer worldwide and the third-most common cause of cancer mortality
Realtime quantitative polymerase chain reaction and western blot analyses revealed that CBX6 mRNA and protein expression levels were both markedly increased in all six hepatocellular carcinoma (HCC) cell lines compared to the THLE-3 cell line (Figure 1A).we detected CBX6 mRNA expression in 50 pairs of primary HCC tissue samples and corresponding adjacent nontumor tissue samples
Our results revealed that CBX6 expression levels were frequently increased in HCC, implying that the protein plays an oncogenic role in the disease
Summary
Primary liver cancer is the fifth-most common cancer worldwide and the third-most common cause of cancer mortality. Hepatocellular carcinoma (HCC) accounts for nearly 90% of primary liver cancers [1, 2]. HCC always develops in the background of chronic hepatitis or cirrhosis. The chromobox (CBX) protein family comprises chromodomain-containing proteins involved in regulating gene expression, cell self-renewal and differentiation [8,9,10,11]. The detailed functions of each protein remain unclear; these proteins play important roles in disease progression. CBX6 shows a high degree of conservation, but its chromodomains display significant differences from those of other proteins with respect to their histone peptide binding preferences. The role of CBX6 in HCC development and progression has not been explored
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