NEK6, a NIMA-related serine/threonine protein kinase, is crucial for mitosis progression, including mitotic spindle formation, metaphase-to-anaphase transition, and centrosome separation. It also has a role in DNA repair and can induce apoptosis when inhibited. It is involved in multiple pathways, such as interacting with FOXO3 to regulate de novo purine synthesis in ovarian cancer [1,2].

Knockout of NEK6 in DU-145 prostate cancer cells decreases clonogenic capacity, proliferation, cell viability, and mitochondrial activity, increases intracellular ROS, and induces apoptosis, suggesting it may be a new strategy for castration-resistant prostate cancer therapy [3]. In macrophages, Nek6 knockdown polarizes them into a pro-inflammatory phenotype via inhibiting STAT3 expression [4]. In reactive astrogliosis, NEK6 is rapidly induced following pathological stimulations, and its enhanced expression promotes reactive astrogliosis while down-regulation dampens it [5]. In osteosarcoma, NEK6 promotes progression via activating the STAT3 signaling pathway, inhibited by miR-26a-5p [6].

In conclusion, NEK6 is essential for mitosis and DNA repair. Model-based research, especially gene knockout in cancer cells and other cell types, reveals its role in various disease-related processes like cancer progression, macrophage polarization, and reactive astrogliosis, offering potential therapeutic targets for diseases such as prostate cancer, ovarian cancer, and osteosarcoma.

References:

1. Panchal, Nagesh Kishan, Mohanty, Shruti, Prince, Sabina Evan. 2022. NIMA-related kinase-6 (NEK6) as an executable target in cancer. In Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 25, 66-77. doi:10.1007/s12094-022-02926-4. https://pubmed.ncbi.nlm.nih.gov/36074296/

2. Liu, Jingchun, Wang, Haoyu, Wan, Huanzhi, Yang, Lian, Hong, Li. 2024. NEK6 dampens FOXO3 nuclear translocation to stabilize C-MYC and promotes subsequent de novo purine synthesis to support ovarian cancer chemoresistance. In Cell death & disease, 15, 661. doi:10.1038/s41419-024-07045-2. https://pubmed.ncbi.nlm.nih.gov/39256367/

3. Pavan, Isadora Carolina Betim, Basei, Fernanda Luisa, Severino, Matheus Brandemarte, Simabuco, Fernando Moreira, Kobarg, Jörg. 2023. NEK6 Regulates Redox Balance and DNA Damage Response in DU-145 Prostate Cancer Cells. In Cells, 12, . doi:10.3390/cells12020256. https://pubmed.ncbi.nlm.nih.gov/36672191/

4. Wu, Xiaoyan, Deng, Ke-Qiong, Cai, Huan-Huan, Lu, Zhibing, Cheng, Wen-Lin. 2023. Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via inhibiting STAT3 expression. In International journal of experimental pathology, 104, 237-246. doi:10.1111/iep.12489. https://pubmed.ncbi.nlm.nih.gov/37431082/

5. Yu, Ying, Shen, Tianjin, Zhong, Xiaoling, Zhang, Zhaohui, Zhang, Chun-Li. 2021. NEK6 is an injury-responsive kinase cooperating with STAT3 in regulation of reactive astrogliosis. In Glia, 70, 273-286. doi:10.1002/glia.24104. https://pubmed.ncbi.nlm.nih.gov/34643969/

6. Zhu, Min, Sun, Yuyu, Xue, Huawei, Gu, Baorong, Yan, Xiaoling. 2023. NEK6 Promotes the Progression of Osteosarcoma Through Activating STAT3 Signaling Pathway by Down-Regulation of miR-26a-5p. In International journal of general medicine, 16, 2831-2848. doi:10.2147/IJGM.S413461. https://pubmed.ncbi.nlm.nih.gov/37426517/