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CircLMTK2 acts as a tumor suppressor in prostate cancer via regulating the expression of microRNA-183. | LitMetric

Background: Prostate cancer (PCa) is one of the commonest male urinary and reproductive system malignancies with high morbidity and mortality. circLMTK2 was reported as a tumor suppressor, therefore, we attempted to investigate the potential mechanism of circLMTK2 in PCa.

Methods: qRT-PCR was employed to examine the expressions of circLMTK2 and miR-183. Afterwards, cell transfection was conducted for overexpressing circLMTK2 and miR-183 in LNCaP and PC3 cells, and silencing circLMTK2 in RWPE1 cells. Then, CCK-8 assay, BrdU, transwell assay, flow cytometry and western blot were respectively conducted to examine the variations of cell growth and metastasis, as well as apoptosis. The expressions of key proteins involved in Wnt/β-catenin and PI3K/AKT pathways were further investigated utilizing western blot.

Results: circLMTK2 was lowly expressed in tumor tissues. circLMTK2 overexpression suppressed cell proliferation and metastasis, however promoted cell apoptosis in LNCaP and PC3 cells. circLMTK2 knockdown enhanced cell viability, proliferation, migration and invasion, while had no significant influences on apoptosis of RWPE1 cells. Further experiments verified that miR-183 up-regulation counteracted the influences triggered by circLMTK2 overexpression in LNCaP and PC3 cells. Besides, it markedly promoted the viability, proliferation, migration and invasion of LNCaP cells, however had no significant influence on cell apoptosis. Moreover, the inhibitory effects on Wnt/β-catenin and PI3K/AKT pathways evoked by circLMTK2 overexpression were diminished by miR-183 up-regulation in LNCaP and PC3 cells.

Conclusion: These outcomes illustrated that circLMTK2 overexpression exerts an anti-tumor effects through down-regulating the expression of miR-183.

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http://dx.doi.org/10.1016/j.lfs.2019.117097DOI Listing

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