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

• Published in: Technology in cancer research & treatment 2019-01, Vol.18, p.1533033819886897-1533033819886897
• Main Authors: Liu, Ming-Kai, Ma, Tao, Yu, Yang, Suo, Yong, Li, Kai, Song, Shi-Chao, Zhang, Wei
• Format: Article
• Language: English
• Subjects: AKT protein; Apoptosis; Apoptosis - genetics; Bladder cancer; Cancer; Cell Cycle - genetics; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; Cell viability; Forkhead Box Protein O1 - genetics; Forkhead Box Protein O1 - metabolism; FOXO1 protein; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Golgi cells; Humans; Membrane Proteins - genetics; Membrane Proteins - metabolism; MicroRNAs; MicroRNAs - genetics; miRNA; Original; Phosphorylation; Polymerase chain reaction; Proto-Oncogene Proteins c-akt - metabolism; RNA Interference; Signal Transduction; Tumor cell lines; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Western blotting
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/1533033819886897

Objective: To investigate role of microRNA-1/Golgi phosphoprotein 3/Foxo1 axis in bladder cancer. Methods: 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. Results: 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. Conclusion: 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.