The tumor suppressor miR-642a-5p targets Wilms Tumor 1 gene and cell-cycle progression in prostate cancer
| Autor: | Andrew J. Woo, Peter J. Leedman, Michael R. Epis, Lisa M. Stuart, Kirsty L. Richardson, Dianne J. Beveridge, Rikki A. M. Brown |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Science IGFBP3 Drug development Mice SCID Biology urologic and male genital diseases Article Prostate cancer Cell Line Tumor LNCaP microRNA medicine Animals Humans RNA Small Interfering WT1 Proteins 3' Untranslated Regions Base Pairing S-Phase Kinase-Associated Proteins Cell Proliferation Monomeric GTP-Binding Proteins Multidisciplinary Oncogene Base Sequence Cell Cycle Intracellular Signaling Peptides and Proteins Prostate Prostatic Neoplasms Wilms' tumor Cell cycle medicine.disease Survival Analysis Xenograft Model Antitumor Assays GPS2 Tumor Burden Gene Expression Regulation Neoplastic Repressor Proteins MicroRNAs Insulin-Like Growth Factor Binding Protein 3 Cancer research Medicine Protein Kinases Signal Transduction |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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