Department of Pharmacology, School of Dentistry, Kyungpook National University, 700-412 Daegu, Korea.
Department of Oral Medicine, School of Dentistry, Kyungpook National University, 700-412 Daegu, Korea.
Cells. 2020 May 28;9(6):1347. doi: 10.3390/cells9061347.
The discovery of novel and critical genes implicated in malignant development is a topic of high interest in cancer research. Intriguingly, a group of genes named "double-agent" genes were reported to have both oncogenic and tumor-suppressive functions. To date, less than 100 "double-agent" genes have been documented. Fubp1 is a master transcriptional regulator of a subset of genes by interacting with a far upstream element (FUSE). Mounting evidence has collectively demonstrated both the oncogenic and tumor suppressive roles of Fubp1 and the debate regarding its roles in tumorigenesis has been around for several years. Therefore, the detailed molecular mechanisms of Fubp1 need to be determined in each context. In the present study, we showed that the Fubp1 protein level was enriched in the S phase and we identified that Fubp1 deficiency altered cell cycle progression, especially in the S phase, by downregulating the mRNA expression levels of genes encoding cyclin A. Although this Fubp1-cyclin A axis appears to exist in several types of tumors, Fubp1 showed heterogeneous expression patterns among various cancer tissues, suggesting it exhibits multiple and complicated functions in cancer development. In addition, we showed that Fubp1 deficiency confers survival advantages to cells against metabolic stress and anti-cancer drugs, suggesting that Fubp1 may play both positive and negative roles in malignant development.
在癌症研究中，发现新的、关键的与恶性发展相关的基因是一个备受关注的话题。有趣的是，一组被称为“双重作用”基因的基因被报道具有致癌和肿瘤抑制功能。迄今为止，只有不到 100 个“双重作用”基因被记录在案。Fubp1 是一组基因的主要转录调控因子，通过与远上游元件（FUSE）相互作用。越来越多的证据表明 Fubp1 具有致癌和肿瘤抑制作用，并且关于其在肿瘤发生中的作用的争论已经存在了几年。因此，需要在每个背景下确定 Fubp1 的详细分子机制。在本研究中，我们表明 Fubp1 蛋白水平在 S 期富集，并且我们鉴定出 Fubp1 缺乏通过下调编码细胞周期蛋白 A 的基因的 mRNA 表达水平来改变细胞周期进程，特别是在 S 期。虽然这个 Fubp1-细胞周期蛋白 A 轴似乎存在于几种类型的肿瘤中，但 Fubp1 在各种癌症组织中的表达模式存在异质性，表明它在癌症发展中表现出多种复杂的功能。此外，我们表明 Fubp1 缺乏赋予细胞在代谢应激和抗癌药物下的生存优势，表明 Fubp1 在恶性发展中可能发挥积极和消极的作用。
