ATBF1 Participates in Dual Functions of TGF-β via Regulation of Gene Expression and Protein Translocalization
ATBF1 Participates in Dual Functions of TGF-β via Regulation of Gene Expression and Protein Translocalization
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ATBF1 通过基因表达和蛋白质转位的调节参与 TGF-β 的双重功能
DOI：
10.3390/biom10050807
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发表时间：
2020-05-01
期刊：
影响因子：
5.5
通讯作者：
Zhao, Jiyuan
中科院分区：
文献类型：
--
作者：
Li, Mei;Zhang, Anqi;Zhao, Jiyuan
TGF-β是调节多种病理生理功能的关键细胞因子。对于肿瘤的发展和进展，据报道TGF-β作为肿瘤抑制剂和上皮-间质转化（EMT）诱导剂发挥双重功能。TGF-β信号通路的作用机制是TGF-β/Smad靶向治疗的基础。在这里，ATBF 1被证明通过不同的方式参与TGF-β的双重功能。一方面，ATBF 1表达水平与TGF-β诱导的EMT和迁移相关。TGF-β处理后，ATBF 1表达以剂量和时间依赖性方式降低，沿着细胞形态和EMT标志物表达发生变化。通过siRNA敲低ATBF 1进一步促进EMT进展和细胞迁移。另一方面，ATBF 1定位与TGF-β抑制的细胞增殖相关。TGF-β激活组ATBF 1核定位细胞数明显高于对照组。之后，通过siRNA敲低ATBF 1挽救了受TGF-β影响的细胞增殖抑制。这些数据表明，ATBF 1是TGF-β双重作用的关键基因，这可能有助于未来的治疗。
TGF-beta is a critical cytokine to regulate multiple pathophysiological functions. For tumor development and progression, TGF-beta was reported to play dual functions as a tumor suppressor and epithelial-mesenchymal transition (EMT) inducer. The mechanism of the TGF-beta signaling pathway is essential for TGF-beta/Smad-targeted therapy in clinic. Here, ATBF1 was demonstrated to participate in dual functions of TGF-beta via different ways. On one hand, ATBF1 expression level was associated with EMT and migration induced by TGF-beta. After TGF-beta treatment, ATBF1 expression was reduced in a dose- and time-dependent manner, along with the alteration of cell morphology and EMT marker expression. Knockdown of ATBF1 by siRNA further promoted EMT progression and cell migration. On the other hand, ATBF1 localization was associated with cell proliferation inhibited by TGF-beta. The number of cells with nucleus localization of ATBF1 in TGF-beta activation group was much higher than that in control group. After that, knockdown of ATBF1 by siRNA rescued the inhibition of cell proliferation affected by TGF-beta. These data revealed that ATBF1 is a key gene for the dual roles of TGF-beta, which may contribute to future therapy.