TGF-β and microRNA Interplay in Genitourinary Cancers.
Joanna BogusławskaPiotr KrystSlawomir PoletajewAgnieszka Piekiełko-WitkowskaPublished in: Cells (2019)
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.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- signaling pathway
- gene expression
- prostate cancer
- dna methylation
- systematic review
- oxidative stress
- ejection fraction
- randomized controlled trial
- pi k akt
- prognostic factors
- climate change
- newly diagnosed
- cell proliferation
- transcription factor
- papillary thyroid
- young adults
- childhood cancer
- cell death
- cell migration
- lymph node metastasis
- high resolution
- benign prostatic hyperplasia
- simultaneous determination
- cancer stem cells