Abstract
Increasing evidence has indicated that thyroid hormone receptor interacting protein 13 (TRIP13) exerts a cancer-promoting role in a broad spectrum of cancers. However, the detailed relevance and function of TRIP13 in cervical cancer remain undefined. The goal of this work was to evaluate the functional significance and mechanism of TRIP13 in cervical cancer. Our data demonstrated that TRIP13 expression was markedly increased in cervical cancer tissue, and high expression of TRIP13 predicted a low survival rate in cervical cancer patients. Knockdown of TRIP13 caused a significant reduction in the proliferation and invasion of cervical cancer cells. By contrast, over-expression of TRIP13 accelerated the proliferation and invasion of cervical cancer cells. Further data revealed that TRIP13 enhanced the activation of Wnt/β-catenin signaling associated with modulation of α-Actinin-4 (ACTN4). Knockdown of ACTN4 markedly reversed TRIP13-mediated activation of Wnt/β-catenin signaling. In addition, inhibition of Wnt/β-catenin signaling reversed TRIP13-induced cancer-promoting effects in cervical cancer cells. Knockdown of TRIP13 markedly retarded the tumor formation and growth of cervical cells in vivo in nude mice. Taken together, the data of this work indicate that TRIP13 accelerates the proliferation and invasion of cervical cancer by enhancing Wnt/β-catenin signaling via regulation of ACTN4. These findings underscore a relevance of the TRIP13/ACTN4/Wnt/β-catenin signaling axis in the progression of cervical cancer and suggest TRIP13 as a potential target for treatment of cervical cancer.