Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan, University, Wuhan, Hubei 430071, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan, University, Wuhan, Hubei 430071, China.
Int J Biol Sci. 2021 May 11;17(8):1995-2008. doi: 10.7150/ijbs.59019. eCollection 2021.
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 . 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.
异常表达和功能障碍的丝氨酸/苏氨酸激酶 Nek2(Never-in-mitosis-A-related kinase 2)可导致肿瘤发生。NEK2 水平升高与恶性进展、耐药性和不良预后有关。然而,NEK2 水平与非小细胞肺癌(NSCLC)的发生之间的关系尚不清楚。本研究旨在探讨 Nek2 对 NSCLC 发生和肿瘤微环境的影响。下调 Nek2 抑制了 A549 和 H1299 细胞的增殖、迁移和侵袭,并将细胞周期阻滞在 G0/G1 期。Nek2 的缺失抑制了肿瘤细胞释放白细胞介素-10(IL-10)、巨噬细胞 M2 样极化、血管生成和血管内皮细胞迁移。此外,Nek2 缺陷抑制了肿瘤生长。总之,下调 Nek2 抑制了 NSCLC、巨噬细胞 M2 极化和血管生成的发生和发展。Nek2 的异常表达不仅可能预示着肿瘤的进展和患者的预后,而且可能成为一个具有巨大发展前景的潜在分子治疗靶点。