NEK2 Control of Esophageal Squamous Cell Carcinoma Growth Based on Circadian Oscillation

Abstract

Esophageal squamous cell carcinoma (ESCC) is a globally prevalent malignancy known for its aggressive nature and unfavorable outcomes. Identifying new biomarkers is crucial for the early detection and improved prognostication of ESCC. The circadian clock and NIMA-related kinase 2 (NEK2) are pivotal in cancer development. While the impact of circadian rhythm disruptions on ESCC progression is evident, the specific contribution of NEK2 to these changes is not well understood. Our study discovered NEK2 as a consistently differentially expressed gene across multiple datasets, with elevated expression in ESCC tissues. Notably, NEK2 overexpression was linked to increased ESCC cell proliferation, whereas its inhibition led to reduced cell growth and proliferation. Pathway analyses, including KEGG and Gene Set Enrichment Analysis (GSEA), indicated NEK2's association with established pathways like the cell cycle, and intriguingly, identified the circadian rhythm as a novel pathway influenced by NEK2. RNA sequencing data demonstrated NEK2's circadian rhythmic expression, and subsequent in vitro experiments confirmed its oscillation in synchronized ESCC cells. Moreover, we found a positive correlation between the efficacy of the NEK2 inhibitor INH6 and NEK2 expression levels in ESCC. In conclusion, our findings position NEK2 as a time-dependent oncogene and a potential biomarker in ESCC, highlighting its role in both tumorigenesis and the circadian rhythm.