MiR-143 Decreases Human Prostate Cancer Cell Proliferation And Migration Through Suppression Of KRAS

Objective: To confirm that persistent decreased levels of miR-143 in prostate cancer cells may be directly involved in carcinogenesis through activation of mitogen-activated protein kinase (MAPK) cascade via KRAS. First investigated the relationship between KRAS expression and miR-143 levels in prostate cancer tissues and then transfect DU145 and PC-3 cells with has-miR-143 mimics to explore the effects on cell proliferation and migration.Materials and Methods: To verify its effect and mechanisms on prostate cancer cell proliferation and migration, miR-143 and its target gene KRAS expression was measured by real-time PCR and western blotting and effects of miR-143 in prostate cancer cell proliferation and migration were evaluated by MTT, colony formation, and transwell migratory assays.Results:1.An inverse correlation of expression between miR-143 and KRAS protein was observed in all prostate cancer samples (Pearson's correlation scatter plots: R = -0.707, P < 0.05).2.The increased expression of miR-143 significantly inhibited the growth of prostate cancer cells in 48h and 72h (both P < 0.05), however no significant inhibition was observed in 24h (P > 0.05). Transfection with miR-143 decreased the plating efficiency of prostate cancer cells (P < 0.05). Interestingly, prostate cancer cells transfected with miR-143 had a 0.3–fold decrease in cell motility.3.KRAS, p-ERK1/2, as well as Cyclin D1, were significantly inhibited by treatment with miR-143 mimics compared with NC mimics . Luciferase activity of the 3'UTR KRAS-Luc construct was decreased in the presence of miR-143 compared with that of NC, whereas luciferase activity of scramble construct was not affected.Conclusion: MiR-143 was frequently downregulated in prostate cancer and is a potential tumor suppressor miRNA for prostate cancer development and progression. miR-143 regulates KRAS, p-ERK1/2 and Cyclin D1 and might have a role in cell proliferation and migration. These findings provide a potential development of a new approach for the treatment of prostate cancer.