Abstract 3085: MicroRNA-186 inhibition alters cell proliferation and colony formation in prostate cancer
| Autor: | LaCreis R. Kidd, Dominique Jones, Katharine R. Hobbing, M. L. Schmidt, Geoffrey J. Clark |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Cancer Research. 75:3085-3085 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2015-3085 |
| Popis: | MicroRNAs (miRs), key regulators of cancer-related genes, are dysregulated in many solid tumors, including prostate cancer. However, the role of miR-186 in prostate cancer (PCA) requires further elucidation. Previously, we observed mature miR-186-5p was significantly up-regulated in the serum collected from PCA patients (n = 15) diagnosed with aggressive PCA (stage III/IV) disease compared to disease-free men (n = 5). In addition, miR-186 expression was significantly up-regulated in metastatic PCA cells (PC3) compared to a normal prostate epithelial cell line (RWPE1). Putative and predicted miR-186 gene targets in various cancers include pro-apoptotic and tumor suppression-related genes (e.g., P2×7, FOXO1, AKAP12). We hypothesized that miR-186 inhibition will reduce the aggressive PCA phenotype. To test this hypothesis, PC3 cells were transiently transfected with miR-186 inhibitor and scramble control for 24hrs. Cell viability and colony formation of transfected cells were evaluated via the ATPlite Luminescence assay and soft agar assay. We also evaluated expression profiles of predicted miR-186 gene targets in PCA cell lines and transiently transfected PC3 cells using qRT-PCR. Transient inhibition of miR-186 repressed cellular proliferation and colony formation by 48-58% in 72-96hrs and 30% after 21 days, respectively. We observed a 1.6-2.24 fold up-regulation in ROCK1 gene expression in PC3 cells treated with miR-186 inhibitor. However, additional studies are needed to assess whether stable inhibition of miR-186 will increase PCA invasiveness by up-regulating ROCK1 using in vitro assays and murine models. Moreover, predicted miR-186 gene targets require validation using qRT-PCR, western blots and luciferase reporter assays. Such efforts may lead to the identification of novel biomarkers to improve diagnostic, prognostic and clinical management strategies. Citation Format: Dominique Zilpha Jones, Katharine R. Hobbing, M. L. Schmidt, Geoffrey J. Clark, LaCreis R. Kidd. MicroRNA-186 inhibition alters cell proliferation and colony formation in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3085. doi:10.1158/1538-7445.AM2015-3085 |
| Databáze: | OpenAIRE |
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