Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China.
Department of comprehensive internal medicine, Affiliated Hospital, Qingdao University, Qingdao, 266003, China.
Mol Cancer. 2018 Jul 25;17(1):104. doi: 10.1186/s12943-018-0856-3.
FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein-protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.
FOXO3a 是叉头框转录因子 FOXO 亚家族的成员，介导多种细胞过程，包括细胞凋亡、增殖、细胞周期进展、DNA 损伤和肿瘤发生。它还响应多种细胞应激，如紫外线照射和氧化应激。FOXO3a 的功能受复杂的过程网络调节，包括 microRNAs (miRNAs) 的转录后抑制、翻译后修饰 (PTMs) 和蛋白质-蛋白质相互作用。FOXO3a 广泛涉及多种疾病，特别是在乳腺癌、肝癌、结肠癌、前列腺癌、膀胱癌和鼻咽癌的恶性肿瘤中。新出现的证据表明，FOXO3a 在癌症中作为肿瘤抑制因子发挥作用。FOXO3a 在癌细胞系中经常通过 FOXO3a 基因突变或 FOXO3a 蛋白的细胞质隔离而失活。其失活与癌症的发生和进展有关。在实验研究中，FOXO3a 的过表达抑制癌细胞的增殖、致瘤潜能和侵袭性，而 FOXO3a 的沉默导致对肿瘤发生的保护作用显著减弱。FOXO3a 在正常生理和癌症发展中的作用给制定癌症的有效治疗策略带来了巨大挑战。在这篇综述中，我们总结了最近的发现，并概述了目前对 FOXO3a 在癌症发展和进展中的影响的理解。
