RING box protein-1 promotes the metastasis of cervical cancer through regulating matrix metalloproteinases via PI3K/AKT signaling pathway

Abstract

Cervical cancer (CC) remains a leading cause of cancer mortality amongst females worldwide. Some of the CC patients may experience early metastases of the primary tumor, however the underlying mechanism remains unclear. Aberrant expression of RING box protein-1 (RBX1), a subunit in the E3 ubiquitin ligase family, has been reported in several cancer types. Nevertheless, little is known regarding the role of RBX1 in the metastasis of CC patients. In this study, we examined the expression of RBX1 from 90 biopsies of CC patients, and found a significantly increased expression of RBX1 in the tumor tissues compared to the normal tissues. Notably, the abundance of RBX1 in the CC patients with metastasis was higher than their counterparts without metastasis, suggesting that RBX1 may play a significant role in the modulation of CC metastasis. Furthermore, by using Hela cells as a model of CC in vitro, we demonstrated that ectopic over-expression of RBX1 could significantly promote the migration and invasion of Hela cells, whereas knockdown of RBX1 could remarkably suppress the migration and invasion of Hela cells. Mechanistically, the regulatory effect of RBX1 on cell metastasis was associated with changes in matrix metalloproteinases (MMP3 and MMP9) and altered activity of PI3K/AKT signaling. In conclusion, this study highlighted RBX1 as a novel target that can promote the metastasis of Hela cells in vitro, which may contribute to the development of alternative therapeutic options for CC patients.