The roles of HOXB8 through activating Wnt/β-catenin and STAT3 signaling pathways in the growth, migration and invasion of ovarian cancer cells.

Abstract

Ovarian cancer is one of the gynecological malignancies ranked third in incidence and first in mortality in the world. Homoboxb8 (HOXB8) has been demonstrated to play crucial roles in various tumors. However, the function of HOXB8 in ovarian cancer remains to be addressed. Quantitative real-time polymerase chain reaction, immunohistochemistry staining and western blot assays demonstrated that HOXB8 expression was up-regulated in human ovarian cancer tissues and cells. The results of CCK-8 and colony formation assays indicated that HOXB8 promoted the proliferation of ovarian cancer cells. Transwell and immunofluorescence (IF) staining assay demonstrated that HOXB8 promoted the migration and invasion of ovarian cancer cells. Importantly, mechanism analysis implied that HOXB8 increased the expression of β-catenin and phosphorylation of STAT3, and the downstream target molecules of Cyclin D1, c-Myc, TWIST1, MMP7 and MMP9, indicating that HOXB8 could promote the activation of Wnt/β-catenin and STAT3 pathways. Moreover, HOXB8 knockdown suppressed xenograft tumor growth, and inhibited the levels of HOXB8 and Ki-67, while increasing the level of E-cadherin in mice. In conclusion, HOXB8 promotes cell proliferation, migration and invasion through modulating Wnt/β-catenin and STAT3 signaling pathways in ovarian cancer, suggesting that HOXB8 may provide a promising target for the therapy of ovarian cancer.