2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Trends Pharmacol Sci. 2012 Jul;33(7):382-93. doi: 10.1016/j.tips.2012.04.003. Epub 2012 May 19.
The activin/transforming growth factor-β (TGF-β) pathway plays an important role in tumorigenesis either by its tumor suppressor or tumor promoting effect. Loss of members of the TGF-β signaling by somatic mutations or epigenetic events, such as DNA methylation or regulation by microRNA (miRNA), may affect the signaling process. Most members of the TGF-β pathway are known to be targeted by one or more miRNAs. In addition, the biogenesis of miRNAs is also regulated by TGF-β both directly and through SMADs. Based on these interactions, it appears that autoregulatory feedback loops between TGF-β and miRNAs influence the fate of tumor cells. Our aim is to review the crosstalk between TGF-β signaling and the miRNA machinery to highlight potential novel therapeutic targets.
激活素/转化生长因子-β(TGF-β)途径通过其肿瘤抑制或促进作用在肿瘤发生中起着重要作用。通过体细胞突变或表观遗传事件(如 DNA 甲基化或 miRNA 调节)丢失 TGF-β 信号的成员可能会影响信号转导过程。大多数 TGF-β 途径成员已知受一种或多种 miRNA 的靶向作用。此外,miRNA 的生物发生也受到 TGF-β 的直接和 SMAD 调节。基于这些相互作用,TGF-β 和 miRNA 之间的自反馈调节环似乎影响肿瘤细胞的命运。我们的目的是综述 TGF-β 信号与 miRNA 机制之间的相互作用,以突出潜在的新治疗靶点。