Song Jiali, Li Longshan, Fang Yang, Lin Yue, Wu Luojia, Wan Wei, Wei Gen, Hua Fuzhou, Ying Jun
Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
Key Laboratory of Anesthesiology of Jiangxi Province, Nanchang City, Jiangxi Province, P.R. China.
Mol Cancer Ther. 2023 Sep 5;22(9):1028-1039. doi: 10.1158/1535-7163.MCT-23-0208.
A growing number of studies have demonstrated that cancer development is closely linked to abnormal gene expression, including alterations in the transcriptional activity of transcription factors. The Forkhead box class N (FOXN) proteins FOXN1-6 form a highly conserved class of transcription factors, which have been shown in recent years to be involved in the regulation of malignant progression in a variety of cancers. FOXNs mediate cell proliferation, cell-cycle progression, cell differentiation, metabolic homeostasis, embryonic development, DNA damage repair, tumor angiogenesis, and other critical biological processes. Therefore, transcriptional dysregulation of FOXNs can directly affect cellular physiology and promote cancer development. Numerous studies have demonstrated that the transcriptional activity of FOXNs is regulated by protein-protein interactions, microRNAs (miRNA), and posttranslational modifications (PTM). However, the mechanisms underlying the molecular regulation of FOXNs in cancer development are unclear. Here, we reviewed the molecular regulatory mechanisms of FOXNs expression and activity, their role in the malignant progression of tumors, and their value for clinical applications in cancer therapy. This review may help design experimental studies involving FOXN transcription factors, and enhance their therapeutic potential as antitumor targets.
越来越多的研究表明，癌症的发展与异常基因表达密切相关，包括转录因子转录活性的改变。叉头框N类（FOXN）蛋白FOXN1 - 6构成了一类高度保守的转录因子，近年来已证明它们参与多种癌症的恶性进展调控。FOXN蛋白介导细胞增殖、细胞周期进程、细胞分化、代谢稳态、胚胎发育、DNA损伤修复、肿瘤血管生成及其他关键生物学过程。因此，FOXN蛋白的转录失调可直接影响细胞生理并促进癌症发展。众多研究表明，FOXN蛋白的转录活性受蛋白质 - 蛋白质相互作用、微小RNA（miRNA）和翻译后修饰（PTM）调控。然而，FOXN蛋白在癌症发展中的分子调控机制尚不清楚。在此，我们综述了FOXN蛋白表达和活性的分子调控机制、它们在肿瘤恶性进展中的作用以及它们在癌症治疗临床应用中的价值。本综述可能有助于设计涉及FOXN转录因子的实验研究，并增强它们作为抗肿瘤靶点的治疗潜力。
