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

AI Article Synopsis

  • The study aimed to explore the role of the microRNA-1/Golgi phosphoprotein 3/Foxo1 axis in bladder cancer, finding that microRNA-1 was downregulated while Golgi phosphoprotein 3 was overexpressed in bladder cancer tissues and cells.
  • Results showed that knocking down Golgi phosphoprotein 3 reduced cell viability and proliferation, increased apoptosis, and caused cell cycle arrest, while overexpressing microRNA-1 had similar inhibitory effects.
  • The findings indicate that microRNA-1 directly targets Golgi phosphoprotein 3, suggesting a potential pathway for therapeutic interventions in bladder cancer.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851605PMC
http://dx.doi.org/10.1177/1533033819886897DOI Listing

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