Overexpressed NEK2 contributes to progression and cisplatin resistance through activating the Wnt/β-catenin signaling pathway in cervical cancer

Cervical cancer ranks as the fourth most common cancer among women, with cisplatin resistance posing a significant challenge to the long-term survival of patients.

NEK2 is upregulated in cervical squamous cell carcinoma (CESC) compared to normal tissues and exhibits higher levels in cisplatin-resistant CESC than in sensitive counterparts, correlating with disease progression and poor prognosis. Thus, NEK2 is implicated in the cisplatin resistance of CESC via the activation of the Wnt/β-catenin signaling pathway, suggesting its potential as a prognostic marker and a novel target for the diagnosis and treatment of cisplatin-resistant CESC.

The roles of NEK2 in cervical cancer were examined through bioinformatics analysis. Transfection efficiency and molecular mechanisms were assessed using real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting (WB). To evaluate cell functions, a series of assays, including cell counting kit-8 (CCK-8), wound healing, transwell, colony formation, and flow cytometry (FCM), were performed on HeLa, SiHa, and HeLa/DDP (cisplatin-resistant) cell lines.

We found that NEK2 is upregulated in cervical cancer tissues compared to normal tissues and is further elevated in cisplatin-resistant cervical cancer compared to cisplatin-sensitive cases. The overexpression of NEK2 is associated with enhanced cancer progression, poorer prognosis, and increased cisplatin resistance in cervical cancer patients. Notably, in the presence of cisplatin, the knockdown of NEK2 inhibited cell viability, proliferation, migration, invasion, and G2/M phase arrest in cervical cancer cells, while also enhancing the sensitivity of cisplatin-resistant cervical cancer cells through the inactivation of the Wnt/β-catenin signaling pathway. Conclusions: NEK2 is upregulated in cervical squamous cell carcinoma (CESC) compared to normal tissues and exhibits higher levels in cisplatin-resistant CESC than in sensitive counterparts, correlating with disease progression and poor prognosis. Thus, NEK2 is implicated in the cisplatin resistance of CESC via the activation of the Wnt/β-catenin signaling pathway, suggesting its potential as a prognostic marker and a novel target for the diagnosis and treatment of cisplatin-resistant CESC.