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Updated: Dec 22, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-185 inhibits prostate cancer angiogenesis induced by the nodal/ALK4 pathway
Youkong Li1, Wen Zhong2, Min Zhu3
1Department of Urology, Jingzhou Central Hospital and The Second Clinical Medical College, Yangtze University, No.60 Jingzhong Road, Jingzhou District, Jingzhou, 434020, Hubei Province, People's Republic of China. liyoukong@126.com.
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.
Insights
Inhibition of angiogenesis via targeting the Nodal/ALK4 pathway with miR-185 offers a novel therapeutic strategy for prostate cancer. Overexpression of miR-185 suppressed tumor growth and angiogenesis by downregulating ALK4.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Prostate cancer progression is linked to angiogenesis.
- The Nodal/ALK4 pathway is implicated in cancer vascularization.
- The roles of Nodal/ALK4 and miR-185 in prostate cancer angiogenesis remain unclear.
Purpose of the Study:
- To investigate the role of Nodal/ALK4 in prostate cancer angiogenesis.
- To explore the anti-angiogenic function of miR-185 in prostate cancer.
- To elucidate the regulatory relationship between Nodal/ALK4 and miR-185.
Main Methods:
- Cell proliferation, migration, and tube formation assays were performed.
- Luciferase reporter assays confirmed miR-185 targeting of ALK4.
- Expression levels of miR-185, ALK4, and VEGF were quantified.
- In vivo xenograft experiments assessed the effects of miR-185 and Nodal.
Main Results:
- Nodal increased VEGF expression and promoted prostate cancer cell proliferation and angiogenesis.
- miR-185 overexpression inhibited prostate cancer cell proliferation and angiogenesis by targeting ALK4.
- miR-185 counteracted Nodal-induced pro-angiogenic effects.
- Overexpression of miR-185 suppressed tumor development in vivo.
Conclusions:
- The Nodal/ALK4 pathway drives angiogenesis in prostate cancer.
- Targeting miR-185 to downregulate ALK4 represents a potential anti-angiogenic strategy.
- This study provides novel insights into prostate cancer mechanisms.
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