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Review
. 2019 Dec 12;8(12):1619.
doi: 10.3390/cells8121619.

TGF-β and microRNA Interplay in Genitourinary Cancers

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Free PMC article
Review

TGF-β and microRNA Interplay in Genitourinary Cancers

Joanna Boguslawska et al. Cells. .
Free PMC article

Abstract

Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the "TGF-β paradox" in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.

Keywords: TGF-β; bladder cancer; diagnosis; genitourinary cancers; microRNA; penile cancer; prostate cancer; renal cancer; testicular cancer; treatment.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
TGF-β maturation. The inactive TGF-β precursor dimerizes and the resulting dimer is cleaved by furin endopeptidase resulting in mature TGF-β and the latency-associated peptide (LAP) that bind non-covalently to produce small latent complex. The latter is next bound by latent TGF-β binding protein (LTBP), resulting in a large latent complex.
Figure 2
Figure 2
MicroRNAs regulating key genes of the TGF-β signaling pathway. MicroRNAs acting in bladder, prostate, and renal cancer are shown in colors (yellow, purple, and red, respectively). The details of miRNA-mediated regulation of the TGF-β signaling pathway are provided in the text

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