Qi Jin-Chun, Yang Zhan, Zhang Yan-Ping, Lu Bao-Sai, Yin Yue-Wei, Liu Kai-Long, Xue Wen-Yong, Qu Chang-Bao, Li Wei
Department of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Front Oncol. 2020 Jan 15;9:1535. doi: 10.3389/fonc.2019.01535. eCollection 2019.
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.
转录因子E2F1调节miR-20b-5p前体的表达，并参与上皮-间质转化（EMT）。转化生长因子-β1（TGF-β1）通过与转化生长因子-β受体2（TGFBR2）结合以激活TGF-β信号传导，从而诱导前列腺癌（PCa）发生EMT。然而，TGFBR2、E2F1和miR-20b-5p在PCa细胞EMT调节中的关系尚不清楚。在本研究中，我们发现PC3和DU145细胞中miR-20b-5p的表达水平明显低于前列腺上皮（RWPE-1）细胞，并且TGF-β1处理进一步下调了这两种细胞系中miR-20b-5p的表达。功能研究表明，miR-20b-5p通过上调E-钙黏蛋白并下调波形蛋白来抑制TGF-β1诱导的PC3和DU145细胞的迁移和侵袭，从而导致TGF-β1诱导的EMT受到抑制。通过功能获得和功能缺失实验表明，E2F1介导TGF-β1对miR-20b-5p表达的调节。此外，荧光素酶活性测定表明，TGFBR2是PCa细胞中miR-20b-5p的直接靶标。这些结果表明，miR-20b-5p、TGFBR2和E2F1形成一个调节环来调节由TGF-β1诱导的EMT。miR-20b-5p/TGFBR2/E2F1轴的一种新的调节机制参与了TGF-β1诱导的PCa细胞EMT，并且miR-20b-5p可能是PCa的潜在治疗靶点。
