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BMC Urology
Published in: BMC Urology 1/2020

01-12-2020 | Prostate Cancer | Research article

miR-185 inhibits prostate cancer angiogenesis induced by the nodal/ALK4 pathway

Authors: Youkong Li, Wen Zhong, Min Zhu, Mengbo Li, Zhenwei Yang

Published in: BMC Urology | Issue 1/2020

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Abstract

Background

Inhibition of angiogenesis in prostatic cancer could be a brand-new method to suppress tumour progression. Nodal/ALK4 has been associated with vascularization in many cancers. However, the relationship between and role of Nodal/ALK4 and miR-185 in human prostatic cancer is still unknown.

Methods

Prostatic cancer DU145 cells and LNCaP cells were used to investigate the angiogenic effect induced by Nodal and the anti-angiogenic roles of miR-185. Colony formation assay, MTT assay, transwell assay and tube formation assay were used to explore cell proliferation, migration and tube-forming ability, respectively. A luciferase reporter assay confirmed the binding relationship between miR-185 and ALK4. The expression levels of miR-185, ALK4 and VEGF were detected by qRT-PCR and Western blotting. The effects of miR-185 and Nodal in prostate cancer were also investigated in animal experiments.

Results

VEGF expression was increased in DU145 cells and LNCaP cells after Nodal incubation, and Nodal activated the proliferation ability of prostatic cancer cells and the migration and tube-forming ability of human umbilical vein endothelial cells (HUVECs), which were all inhibited by treatment with the Nodal inhibitor SB431524. Bioinformatics analysis and luciferase assay were used to verify miR-185 as a target of ALK4. Prostatic cancer cell proliferation was inhibited by overexpression of miR-185, which was shown to regulate the migration and angiogenesis of HUVECs by targeting ALK4 for suppression. miR-185 also showed a significant inverse correlation with Nodal treatment and reversed the angiogenic effects induced by Nodal. More importantly, for the first time, xenograft experiments indicated that overexpression of miR-185 suppressed tumour development.

Conclusion

The Nodal/ALK4 pathway is important in the angiogenesis of prostate cancer and can be inhibited by targeting miR-185 to downregulate ALK4. These findings provide a new perspective on the mechanism of prostate cancer formation.
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Metadata
Title
miR-185 inhibits prostate cancer angiogenesis induced by the nodal/ALK4 pathway
Authors
Youkong Li
Wen Zhong
Min Zhu
Mengbo Li
Zhenwei Yang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2020
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/s12894-020-00617-2

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