Abstract
Background
High-mobility group box-1 (HMGB1), originally characterized as a non-histone, nuclear DNA-binding protein, acts as a crucial proinflammatory cytokine, mediating a broad range of inflammatory responses as a secretory form. Recently, it has been reported to be involved in the tumorigenesis and progression of various types of malignancies, but it is unclear whether HMGB1 plays an important role in the progression of esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the significance of HMGB1 in ESCC.
Methods
The tissue and plasma samples were obtained from ESCC patients at before or after operative period and healthy volunteers. The ESCC cell lines and normal human cell lines, such as fibroblast (WI-38) or Human umbilical vein endothelial cell (HUVEC), were used in vitro analyses. The expression levels of HMGB1 in tissue samples were measured by quantitative RT-PCR. The protein levels of HMGB1 were measured using the HMGB1 enzyme-linked immunosorbent assay kit in plasma samples, and using immunohistochemical staining or western blotting in tissue samples or cell lines. The functions of HMGB1 on the ESCC cell lines were investigated by proliferation, invasion, or migration assays.
Results
The mRNA and protein expression of HMGB1 in ESCC tissue was significantly higher than that in paired non-cancerous esophageal mucosa tissue. Plasma HMGB1 level was slightly higher, but not significant, in ESCC patients than in healthy volunteers. However, it was significantly higher in ESCC patients with Neoadjuvant chemotherapy (NAC) than in those without NAC. The mRNA and protein expression of HMGB1 were higher in ESCC cell lines than in WI-38 or HUVEC. In ESCC cells with high HMGB1 expression, knockdown of HMGB1 using specific siRNAs inhibited the cell proliferation, migration and invasion.
Conclusion
These findings suggest that HMGB1 plays a crucial role in tumor malignant potential through its overexpression in esophageal squamous cell carcinoma.
Disclosure
All authors have declared no conflicts of interest.
Prognostic implications and oncogenic roles of MYBL2 protein expression in esophageal squamous-cell carcinoma
