Department of Molecular Bone Biology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
Japan Society for the Promotion of Science, 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan.
Cells. 2023 Apr 10;12(8):1122. doi: 10.3390/cells12081122.
The RUNX transcription factors are frequently dysregulated in human cancers, suggesting their potential as attractive targets for drug treatment. However, all three transcription factors have been described as both tumor suppressors and oncogenes, indicating the need to determine their molecular mechanisms of action. Although RUNX3 has long been considered a tumor suppressor in human cancers, several recent studies have shown that RUNX3 is upregulated during the development or progression of various malignant tumors, suggesting it may act as a "conditional" oncogene. Resolving this paradox and understanding how a single gene can exhibit both oncogenic and tumor-suppressive properties is essential for successful drug targeting of RUNX. This review describes the evidence for the activities of RUNX3 in human cancer and proposes an explanation for the duality of RUNX3 involving the status of p53. In this model, deficiency causes RUNX3 to become oncogenic, leading to aberrant upregulation of MYC.
RUNX 转录因子在人类癌症中经常失调，这表明它们有可能成为药物治疗的有吸引力的靶点。然而，所有这三种转录因子都被描述为既是肿瘤抑制因子又是癌基因，这表明需要确定它们的分子作用机制。虽然 RUNX3 长期以来一直被认为是人类癌症中的肿瘤抑制因子，但最近的几项研究表明，RUNX3 在各种恶性肿瘤的发生或进展过程中被上调，表明它可能作为一种“条件性”癌基因发挥作用。解决这一矛盾并理解单个基因如何表现出致癌和肿瘤抑制特性对于成功靶向 RUNX 至关重要。本文综述了 RUNX3 在人类癌症中的活性证据，并提出了一个涉及 p53 状态的 RUNX3 双重性的解释。在该模型中， 缺失导致 RUNX3 致癌，导致 MYC 异常上调。
