HOXA5 inhibits the proliferation and metastasis of cervical squamous cell carcinoma by suppressing the β-catenin/Snail signaling

Wan-Yu Jin, Yan Zhang, Jia Tian, Long-Kuan Xu, Heng-Jie Lin, Yu-Zhong Yang, Xue-Mei Zhang, Mei-Hua Jin, Wen-Fa Mo, Guang-Ying Qi,  Ying-Qiong Zhou

Abstract:

HOXA5, as a transcription factor, plays an important role in a variety of malignant tumors. Nevertheless, its biological role in cervical squamous cell carcinoma (CSCC) is largely unknown. In our study, we aimed to explore the function of HOXA5 in CSCC and its molecular mechanism. Immunohistochemistry showed that HOXA5 expression was downregulated in human CSCC tissues and HOXA5 staining was negatively correlated with tumor size and histological grade of CSCC. Ectopic expression of HOXA5 inhibited proliferative and metastatic abilities of CSCC cells in vitro and in vivo. Furthermore, overexpression of HOXA5 inhibited the cell cycle by arresting the S/G2 phase by flow cytometry and that was related to the downregulation of Cyclin A. Further study showed that HOXA5 suppressed EMT by inhibiting the β-catenin/Snail signaling resulting in reduced metastasis of CSCC cells. Altogether, our results suggested that HOXA5 inhibited the proliferation and metastasis via repression of the β-catenin/Snail pathway, proposing the potential role of HOXA5 in the prevention and treatment of CSCC.