MiR-1/GOLPH3/Foxo1 Signaling Pathway Regulates Proliferation of Bladder Cancer

Published on 2019-11-13T13:07:29Z (GMT) by
<div>Objective:<p>To investigate role of microRNA-1/Golgi phosphoprotein 3/Foxo1 axis in bladder cancer.</p>Methods:<p>The expression of Golgi phosphoprotein 3 was determined in both bladder cancer tissues and cell lines using quantitative real-time polymerase chain reaction and Western blotting, respectively. Golgi phosphoprotein 3 was knocked down by small hairpin RNA. MicroRNA-1 was overexpressed or inhibited by microRNA-1 mimic or inhibitor. Cell viability and proliferation were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and colony-formation assay. Cell apoptosis and cycle was detected using flow cytometer. The expression of microRNA-1 and Golgi phosphoprotein 3 was determined using quantitative real-time polymerase chain reaction and Western blotting was used to test the expression of Golgi phosphoprotein 3, Foxo1, p-Foxo1, AKT, p-AKT, p27, and CyclinD1. Binding between microRNA-1 and Golgi phosphoprotein 3 was confirmed by Dual-Luciferase Reporter Assay.</p>Results:<p>MicroRNA-1 was downregulated in bladder cancer tissues, while Golgi phosphoprotein 3 was overexpressed in bladder cancer cells and tissues. In both bladder cancer 5637 and T24 cell lines, the cell viability and proliferation were dramatically reduced when Golgi phosphoprotein 3 was knocked down. The inhibition of Golgi phosphoprotein 3 remarkably promoted cell apoptosis and induced cell-cycle arrest, as well as decreased the expression of p-Foxo1, p-AKT, and CyclinD1 and increased the expression of p27. The overexpression of microRNA-1 significantly inhibited cell viability and proliferation, induced G-S cell-cycle arrest, and decreased the expression of Golgi phosphoprotein 3, p-Foxo1, and CyclinD1 and upregulated p27, while inhibition of microRNA-1 led to opposite results. Golgi phosphoprotein 3 was a direct target for microRNA-1.</p>Conclusion:<p>Overexpression of microRNA-1 inhibited cell proliferation and induced cell-cycle arrest of bladder cancer cells through targeting Golgi phosphoprotein 3 and regulation of Foxo1.</p></div>

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Liu, Ming-Kai; Ma, Tao; Yu, Yang; Suo, Yong; Li, Kai; Song, Shi-Chao; et al. (2019): MiR-1/GOLPH3/Foxo1 Signaling Pathway Regulates Proliferation of Bladder Cancer. SAGE Journals. Collection. https://doi.org/10.25384/SAGE.c.4737311.v1