Yanyu Li,1– 4,* Li Cai,2,3,* Jiayun Zhou,2– 4,* Xuping Zhang,2– 4 Yunuo Zheng,2– 4 Jingbo Zhang,2– 4 Hui Cheng,2– 4 Qing Wang,2– 4 Bei Zhang1– 4 

1Suzhou Medical College of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Gynecology and Obstetrics, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Gynecology and Obstetrics, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Gynecology and Obstetrics, Xuzhou Central Hospital Affiliated to Southeast University, Xuzhou, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Bei Zhang, Email bettyzhang10@163.com Qing Wang, Email qingzi4310513@126.com

Purpose: The fourth most common cause of cancer-related deaths in women is cervical cancer. Though treatment of early-stage cervical cancer is often effective, middle and advanced stage cervical cancer is hard to treat and prone to recurrence. We sought to explore the mechanism underlying cervical cancer progression to identify new therapeutic approaches.
Methods: Label-free mass spectrometry (LC-MS/MS) was used to identify differentially expressed proteins in cervical cancer and normal tissues. The findings were confirmed by Western blotting, RT-qPCR, and immunohistochemistry. The function of RCN1 in tumor invasion, metastasis, and proliferation was investigated using in vitro and in vivo tests. Immunoprecipitation tandem mass spectrometry (IP-MS) was performed in RCNI knockdown cells to identify downstream pathways. Western blotting was used for detecting the expressions of the key proteins included in KIF14 and PI3K-AKT-mTOR signaling pathways before and after RCN1 knockout.
Results: RCN1 expression is elevated in patients with lymph node metastases and recurrent cervical cancer and correlates with poor prognosis. Knockdown and overexpression assays revealed that RCN1 promotes proliferation, migration and invasion of cervical cancer cells. RCN1 overexpression encourages metastasis in a mouse xenograft model. Furthermore, RCN1 targets KIF14, an activator of AKT, thus providing a molecular basis that could explain the malignant behavior of RCN1-expressing cervical cancer.
Conclusion: RCN1 is significantly expressed in cervical cancer, which is associated with a poor prognosis, spread and recurrence. By promoting KIF14-induced activation of the PI3K-AKT-mTOR pathway, RCN1 may facilitate the malignant development of cervical cancer.

Keywords: RCN1, KIF14, cervical cancer, PI3K-AKT-mTOR pathway, label-free mass spectrometry