MicroRNA Control of TGF-β Signaling.
Hiroshi I SuzukiPublished in: International journal of molecular sciences (2018)
Transcriptional and post-transcriptional regulation shapes the transcriptome and proteome changes induced by various cellular signaling cascades. MicroRNAs (miRNAs) are small regulatory RNAs that are approximately 22 nucleotides long, which direct the post-transcriptional regulation of diverse target genes and control cell states. Transforming growth factor (TGF)-β family is a multifunctional cytokine family, which plays many regulatory roles in the development and pathogenesis of diverse diseases, including fibrotic disease, cardiovascular disease and cancer. Previous studies have shown that the TGF-β pathway includes the miRNA pathway as an important component of its downstream signaling cascades. Multiple studies of epithelial⁻mesenchymal transition (EMT)-related miRNAs have highlighted that miRNAs constitute the intrinsic bistable molecular switches of cell states by forming double negative feedback loops with EMT-inducing transcription factors. This may be important for understanding the reversibility of EMT at the single-cell level, the presence of distinct EMT transition states and the intra- and inter-tumor heterogeneity of cancer cell phenotypes. In the present review, I summarize the connection between TGF-β signaling and the miRNA pathway, placing particular emphasis on the regulation of miRNA expression by TGF-β signaling, the modulation of TGF-β signaling by miRNAs, the miRNA-mediated modulation of EMT and endothelial⁻mesenchymal transition as well as the crosstalk between miRNA and TGF-β pathways in the tumor microenvironment.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- single cell
- signaling pathway
- cardiovascular disease
- transcription factor
- gene expression
- rna seq
- stem cells
- genome wide
- mesenchymal stem cells
- bone marrow
- high throughput
- poor prognosis
- metabolic syndrome
- idiopathic pulmonary fibrosis
- cancer therapy
- systemic sclerosis
- cardiovascular risk factors
- dna methylation
- drug induced
- lymph node metastasis
- case control