Effect of High-mobility Group Box-1 on Expression of Stem Cell Markers OCT4, Sox2 and Nanog in Cervical Carcinoma

Abstract

Objective To investigate the role of High-mobility group box-1 (HMGB1) protein in regulating the expression of cancer stem cell markers Nanog, OCT4 and Sox2. Methods We transferred recombinant plasmid and target-specific siRNA of HMGB1 into cervical cancer cells. The expression of cancer stem cell markers (OCT4, Sox2 and Nanog) were measured by Western blot and flow cytometry. Immunohistochemical method was applied to detect HMGB1, OCT4, Sox2 and Nanog expression in 66 cases of cervical tissues. Rank correlation analysis was used to analyze their correlation. Results The full-length coding sequence of HMGB1 was 648 bp and recombined to overexpress the plasmid GV230. The selection of the highest interference rate was carried out for subsequent experiments. The protein expression and rates of stem cell markers OCT4, Sox2 and Nanog were significantly higher in HMGB1 overexpression group than those in low HMGB1 expression group and empty vector group(P < 0.05). The protein expression and rates of stem cell markers OCT4, Sox2 and Nanog were significantly lower in low HMGB1 expression group than those in HMGB1 overexpression group and empty vector group(P < 0.05). HMGB1, OCT4, Sox2 and Nanog protein expression in cervical carcinoma tissues were higher than those in chronic cervicitis tissues. Positive correlations were also found between HMGB1 and OCT4, Sox2 and Nanog expression. Conclusion HMGB1 could regulate the expression of cancer stem cell markers Nanog, OCT4 and Sox2, therefore, it is probably a potential target for anti-tumor therapy.

Keywords

• cervical carcinoma
• high-mobility group box-1
• oct4
• nanog
• sox2
• tumor stem cells(tscs)