miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer

Abstract

The transcription factor E2F1 regulates the expression of the miR-20b-5p precursor and is involved in epithelial-to-mesenchymal transition (EMT). Transforming growth factor-β1 (TGF-β1) induces EMT in prostate cancer (PCa) by binding to TGF-beta receptor 2 (TGFBR2) to activate TGF-β signaling. However, the relationship between TGFBR2, E2F1, and miR-20b-5p in the modulation of EMT in PCa cells remains unknown. In this study, we found that the level of miR-20b-5p expression was significantly lower in PC3 and DU145 cells than that in prostate epithelial (RWPE-1) cells, and TGF-β1 treatment further down-regulated miR-20b-5p expression in these two cell lines. Functional studies showed that miR-20b-5p suppressed TGF-β1-induced migration and invasion of PC3 and DU145 cells by up-regulating E-cadherin and down-regulating vimentin, leading to TGF-β1-induced inhibition of EMT. Using gain and loss of function experiments, it was shown that E2F1 mediated TGF-β1 regulation of miR-20b-5p expression. Further, a luciferase activity assay showed that TGFBR2 was a direct target of miR-20b-5p in PCa cells. These results suggest that miR-20b-5p, TGFBR2, and E2F1 form a regulatory loop to modulate EMT induced by TGF-β1. A novel regulatory mechanism underlying the miR-20b-5p/TGFBR2/E2F1 axis is involved in TGF-β1-induced EMT of PCa cells, and miR-20b-5p may be a potential therapeutic target for PCa.

Clinical utility of TGFB1 and its receptors (TGFBR1 and TGFBR2) in thyroid nodules: evaluation based on single nucleotide polymorphisms and mRNA analysis

“…Significantly higher TGFBR1 mRNA levels were found in breast cancer patients with poor prognosis and small tumors as loss of TGFBR2 mRNA was evidenced in primary breast tumors, but, curiously, higher levels of this gene were associated with better prognosis (39), which, added to in vivo and in vitro esophageal squamous cell carcinoma experiments, suggested that TGFBR2 overexpression induces cell cycle arrest and suppress cell growth (40). Furthermore, recent research in cancer cell lines suggested that some miRNAs, such as miR-133b and miR-20b-5p, can inhibit the epithelial-mesenchymal transition (EMT) induced by TGF-β1 by targeting, respectively, TGFBR1 and TGFBR2 genes (41,42). As elucidated by Fuziwara and cols.…”

MicroRNA-363-3p promote the development of acute myeloid leukemia with RUNX1 mutation by targeting SPRYD4 and FNDC3B

“…[ 31 ] MiR-151a-5p was significantly over-expressed in colorectal cancer [ 32 ] and lung cancer. [ 33 ] MiR-20b-5p played an significant role in prostate cancer(Pca), [ 34 ] lung cancer, [ 35 ] laryngeal squamous cell carcinoma, [ 36 ] renal cell carcinoma, [ 37 ] cancer stem cells, [ 38 ] and so on. Nevertheless, there were a few studies involving miR-363-3p in AML.…”

Identification of miRNA-Mediated Subpathways as Prostate Cancer Biomarkers Based on Topological Inference in a Machine Learning Process Using Integrated Gene and miRNA Expression Data

“…Research has shown that induction of miR-106b plays a crucial role in the suppression of the proliferation of prostate cancer cells in a process that involves the TGF-beta signaling pathway ( Zhang et al, 2012 ). Additionally, in human prostate cancer, miR-20b targets and downregulates TGFBR2, which in turn affects Smad2 activation and E2F1 expression, dysregulating the miR-20b-5p expression and contributing to TGF-β-induced epithelial-to-mesenchymal transition ( Qi et al, 2019 ).…”