Document Type
Journal Article
Publication Title
Scientific Reports
Volume
11
Issue
1
Publisher
Nature
School
School of Medical and Health Sciences
RAS ID
36965
Funders
National Health and Medical Research Council / Prostate Cancer Foundation of Australia
Abstract
RNA-based therapeutics are emerging as innovative options for cancer treatment, with microRNAs being attractive targets for therapy development. We previously implicated microRNA-642a-5p (miR-642a-5p) as a tumor suppressor in prostate cancer (PCa), and here we characterize its mode of action, using 22Rv1 PCa cells. In an in vivo xenograft tumor model, miR-642a-5p induced a significant decrease in tumor growth, compared to negative control. Using RNA-Sequencing, we identified gene targets of miR-642a-5p which were enriched for gene sets controlling cell cycle; downregulated genes included Wilms Tumor 1 gene (WT1), NUAK1, RASSF3 and SKP2; and upregulated genes included IGFBP3 and GPS2. Analysis of PCa patient datasets showed a higher expression of WT1, NUAK1, RASSF3 and SKP2; and a lower expression of GPS2 and IGFBP3 in PCa tissue compared to non-malignant prostate tissue. We confirmed the prostatic oncogene WT1, as a direct target of miR-642a-5p, and treatment of 22Rv1 and LNCaP PCa cells with WT1 siRNA or a small molecule inhibitor of WT1 reduced cell proliferation. Taken together, these data provide insight into the molecular mechanisms by which miR-642a-5p acts as a tumor suppressor in PCa, an effect partially mediated by regulating genes involved in cell cycle control; and restoration of miR-642-5p in PCa could represent a novel therapeutic approach.
DOI
10.1038/s41598-021-97190-x
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Beveridge, D. J., Richardson, K. L., Epis, M. R., Brown, R. A. M., Stuart, L. M., Woo, A. J., & Leedman, P. J. (2021). The tumor suppressor miR-642a-5p targets Wilms tumor 1 gene and cell-cycle progression in prostate cancer. Scientific Reports, 11, article 18003. https://doi.org/10.1038/s41598-021-97190-x