TGF-β-Regulated MicroRNAs and Their Function in Cancer Biology.
The transforming growth factor-β (TGF-β) is known to regulate a large number of biological processes and is involved in various aspects of tumor development. Recent studies have shown that the biogenesis of miRNAs can be regulated by TGF-β signaling directly via Smad-dependent mechanisms and/or other unknown mechanisms, which may induce autoregulatory feedback loops in response to the activation of TGF-β signaling, influencing the fate of tumor cells. In this chapter, we summarize the currently described mechanisms underlying TGF-β's regulation of miRNA biogenesis, and the functional role of TGF-β-regulated miRNAs in tumor initiation, epithelial-mesenchymal transition, and tumor microenvironment modulation. Finally, we introduce methods to study TGF-β-regulated miRNAs and their functions in tumor progression and metastasis using an example of publication from our lab demonstrating the presence of a TGF-β-miR-34a-CCL22 signaling axis, which serves as a potent etiological pathway for the development of hepatocellular carcinoma venous metastases.