Int J Biol Sci 2021; 17(8):1995-2008. doi:10.7150/ijbs.59019

Research Paper

NEK2 plays an active role in Tumorigenesis and Tumor Microenvironment in Non-Small Cell Lung Cancer

Rui Bai1*, Cheng Yuan1*, Wenjie Sun1, Jianguo Zhang1, Yuan Luo1, Yanping Gao1, Yangyi Li1, Yan Gong2,3✉, Conghua Xie1,4,5✉

1. Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan, University, Wuhan, Hubei 430071, China.
2. Department of Biological Repositories, Zhongnan Hospital of Wuhan, University, Wuhan, Hubei 430071, China.
3. Tumor Precision Diagnosis and Treatment Technology and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
4. Hubei Key Laboratory of Tumour Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
5. Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
*These authors contributed equally to this work.

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Citation:
Bai R, Yuan C, Sun W, Zhang J, Luo Y, Gao Y, Li Y, Gong Y, Xie C. NEK2 plays an active role in Tumorigenesis and Tumor Microenvironment in Non-Small Cell Lung Cancer. Int J Biol Sci 2021; 17(8):1995-2008. doi:10.7150/ijbs.59019. Available from https://www.ijbs.com/v17p1995.htm

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Abstract

Abnormal expression and dysfunction of Never-in-mitosis-A-related kinase 2 (NEK2) result in tumorigenesis. High levels of NEK2 are related to malignant progression, drug resistance, and poor prognosis. However, the relationship between NEK2 levels and the occurrence of non-small cell lung cancer (NSCLC) remains unknown. This study aimed to explore the impacts of NEK2 on the oncogenesis of NSCLC and the tumor microenvironment. Downregulation of NEK2 inhibited A549 and H1299 cell proliferation, migration, and invasion, blocking cell cycle at the G0/G1 phase. Loss of NEK2 inhibited the release of IL-10 from tumor cells, M2-like polarization of macrophages, angiogenesis, and vascular endothelial cell migration. Furthermore, NEK2 deficiency inhibited tumor growth in vivo. Taken together, NEK2 knockdown inhibited the occurrence and development of NSCLC, M2 polarization of macrophages, and angiogenesis. The abnormal expression of NEK2 might not only indicate tumor progression and patient prognosis but also serve as a potential molecular therapeutic target with great development prospects.

Keywords: NEK2, NSCLC, tumorigenesis, Wnt/β-catenin, tumor microenvironment