Xia Jiliang, Zhao Hongyan, Edmondson Jacob L, Koss Brian, Zhan Fenghuang
Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Cancer Research Institute, Hengyang Medical School, University of South China, Changshengxi Road 28, Hengyang, 421001, Hunan, China.
Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Cancer Research Institute, Hengyang Medical School, University of South China, Changshengxi Road 28, Hengyang, 421001, Hunan, China.
Trends Mol Med. 2025 Jan;31(1):79-93. doi: 10.1016/j.molmed.2024.07.013. Epub 2024 Aug 24.
Never in mitosis A (NIMA)-related kinase 2 (NEK2) is a serine/threonine kinase found in the nucleus and cytoplasm throughout the cell cycle. NEK2 is overexpressed in many cancers and is a biomarker of poor prognosis. Factors contributing to NEK2 elevation in cancer cells include oncogenic transcription factors, decreased ubiquitination, DNA methylation, and the circular RNA (circRNA)/long noncoding RNA (lncRNA)-miRNA axis. NEK2 overexpression produces chromosomal instability and aneuploidy, thereby enhancing cancer progression and suppressing antitumor immunity, which highlights the prominence of NEK2 in tumorigenesis and tumor progression. Small-molecule inhibitors targeting NEK2 have demonstrated promising therapeutic potential in vitro and in vivo across various cancer types. This review outlines the regulatory mechanisms of NEK2 expression, emphasizes its functional roles in cancer initiation and progression, and highlights the anticancer properties of NEK2 inhibitors.
有丝分裂A期相关激酶2（NEK2）是一种丝氨酸/苏氨酸激酶，在整个细胞周期中存在于细胞核和细胞质中。NEK2在许多癌症中过度表达，是预后不良的生物标志物。导致癌细胞中NEK2升高的因素包括致癌转录因子、泛素化减少、DNA甲基化以及环状RNA（circRNA）/长链非编码RNA（lncRNA）-微小RNA（miRNA）轴。NEK2的过度表达会导致染色体不稳定和非整倍体，从而促进癌症进展并抑制抗肿瘤免疫，这突出了NEK2在肿瘤发生和肿瘤进展中的重要性。靶向NEK2的小分子抑制剂在体外和体内对各种癌症类型均显示出有前景的治疗潜力。本综述概述了NEK2表达的调控机制，强调了其在癌症起始和进展中的功能作用，并突出了NEK2抑制剂的抗癌特性。
