High-mobility group box 1-induced epithelial-mesenchymal transition of ovarian cancer through Smad3/Snail/NF-κB pathways

Objective: Our aim was to explore the mechanism of HMGB1 induced epithelial-mesenchymal transition (EMT) in ovarian cancer. Method: Expression of HMGB1 in ovarian cancer and adjacent normal tissues were measured by immunohistochemistry. Over-all survival (OS) and disease-free survival (DFS) was analyzed by the Kaplan-Meier method. Ovarian cancer cell lines OVCAR3 and SKOV3 were transfected with HMGB1 overexpression or HMGB1 knockdown lentiviral vectors, respectively. Epithelial and mesenchymal markers were visualized by immunofluorescence staining and cell invasion and migration ability was assayed by transwell chamber and wound healing assay. Expression of mRNA or proteins were also measured. Results: HMGB1 was significantly upregulated in ovarian cancer tissues. In addition, HMGB1 expression was significantly associated with FIGO stage, histologic grade, and lymph node metastasis. Kaplan-Meier survival analysis showed that high expression of HMGB1 had poorer OS and DFS in ovarian cancer patients. We further found that HMGB1 induced EMT and promoted cell migration and invasion of ovarian cancer cells in vitro and these effects were attenuated by inhibiting expression of HMGB1. Moreover, Smad3/Snail/NF-KB signaling pathways may contribute to regulation of HMGBl-mediated EMT of ovarian cancer cells Conclusion: HMGB1 acts as a promoter of ovarian cancer EMT via activation of Smad3/ Snail/NF-KB pathways.