Objective: MAPK kinase 1 (MEK1) plays an important role in regulating cell proliferation and apoptosis through activation of the ERK/MAPK signaling pathway. It was found that the expression of miR-195 in bladder cancer was abnormally decreased, suggesting that miR-195 may affect the development of bladder cancer. In this study, we examined the expression of miR-195 and MEK1 in bladder cancer tissues and analyzed the relationship between miR-195 and MEK1 in cell proliferation and apoptosis in bladder cancer cells.
Patients and methods: The expression of MEK1 in bladder cancer tissues was detected by western blot, and the expression levels of miR-195 and MEK1 mRNA were detected by qRT-PCR. Log Rank test was used to compare the survival and prognosis of patients with low and high expression of miR-195 and MEK1 by using the median expression of miR-195 and MEK1. Bioinformatics analysis and double luciferase reporter gene test were used to verify the relationship between miR-195 and MEK1. Bladder cancer BIU-87 and 5637 cells were cultured in vitro and divided into two groups: miR-NC group and miR-195 mimic group. The expression of MEK1 and p-MEK1 protein was detected by western blot, apoptosis was detected by flow cytometry, and cell proliferation was detected by EdU staining.
Results: Compared with normal bladder tissue, expression of miR-195 in bladder cancer tissue was significantly decreased, while the expression of MEK1 mRNA and protein was significantly increased. The prognosis of patients with low expression of miR-195 was worse than those with high expression of miR-195. The prognosis of patients with low expression of MEK1 was better than those with high expression of MEK1. Bioinformatics analysis showed that there was a target complementary binding site between miR-195 and MEK1. Double luciferase reporter gene experiments confirmed that there was a target regulatory relationship between miR-195 and MEK1. miR-195 mimic transfection could significantly down-regulate the expression of MEK1 and p-MEK1 proteins in BIU-87 and 5637 cells, weaken cell proliferation, and increase cell apoptosis.
Conclusion: Overexpression of miR-195 can inhibit the proliferation of bladder cancer cells by inhibiting MEK1, which provides further evidence for developing therapy against bladder cancer.
Keywords: MEK1; apoptosis; bladder cancer; miR-195; prognosis; proliferation.
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