Li Yanyu, Cai Li, Zhou Jiayun, Zhang Xuping, Zheng Yunuo, Zhang Jingbo, Cheng Hui, Wang Qing, Zhang Bei
Suzhou Medical College of Soochow University, Suzhou, Jiangsu, People's Republic of China.
Department of Gynecology and Obstetrics, Xuzhou Central Hospital, Xuzhou, Jiangsu, People's Republic of China.
Int J Gen Med. 2025 Sep 2;18:5047-5062. doi: 10.2147/IJGM.S531003. eCollection 2025.
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.
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.
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.
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.
宫颈癌是女性癌症相关死亡的第四大常见原因。尽管早期宫颈癌的治疗通常有效，但中晚期宫颈癌难以治疗且容易复发。我们试图探索宫颈癌进展的机制，以确定新的治疗方法。
采用无标记质谱法（LC-MS/MS）鉴定宫颈癌组织和正常组织中差异表达的蛋白质。通过蛋白质免疫印迹法、逆转录定量聚合酶链反应（RT-qPCR）和免疫组织化学法对研究结果进行验证。利用体外和体内试验研究了 reticulocalbin-1（RCN1）在肿瘤侵袭、转移和增殖中的作用。在RCN1基因敲低的细胞中进行免疫沉淀串联质谱分析（IP-MS），以鉴定下游信号通路。在RCN1基因敲除前后，采用蛋白质免疫印迹法检测驱动蛋白家族成员14（KIF14）和磷脂酰肌醇-3激酶-蛋白激酶B-哺乳动物雷帕霉素靶蛋白（PI3K-AKT-mTOR）信号通路中关键蛋白的表达。
RCN1在有淋巴结转移和复发性宫颈癌患者中表达升高，且与预后不良相关。基因敲低和过表达试验表明，RCN1促进宫颈癌细胞的增殖、迁移和侵袭。RCN1过表达促进小鼠异种移植模型中的转移。此外，RCN1靶向AKT的激活剂KIF14，从而为RCN1表达的宫颈癌的恶性行为提供了分子基础。
RCN1在宫颈癌中显著表达，这与预后不良、扩散和复发有关。通过促进KIF14诱导的PI3K-AKT-mTOR信号通路激活，RCN1可能促进宫颈癌的恶性发展。
