Stromal‐induced downregulation of miR‐1247 promotes prostate cancer malignancy
| Autor: | Giuseppina Comito, Giovanni Raugei, Elisa Giannoni, Maria Letizia Taddei, Matteo Ramazzotti, Andrea Morandi, Lorenzo Cavallini, Laura Pietrovito, Paola Chiarugi |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Epithelial-Mesenchymal Transition Stromal cell Physiology Clinical Biochemistry 03 medical and health sciences Prostate cancer 0302 clinical medicine Downregulation and upregulation anoikis resistance cancer-associated fibroblast miR-1247 neuropilin-1 prostate cancer Cell Biology medicine Humans Neoplasm Invasiveness Anoikis Epithelial–mesenchymal transition Epidermal growth factor receptor Neoplasm Metastasis Cell Proliferation biology Prostatic Neoplasms Cancer Cellular Reprogramming medicine.disease Neuropilin-1 Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Tumor progression 030220 oncology & carcinogenesis Cancer research biology.protein Stromal Cells |
| Zdroj: | Journal of Cellular Physiology. 234:8274-8285 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.27679 |
| Popis: | Cancer progression is strictly dependent on the relationship between tumor cells and the surrounding stroma, which supports cancer malignancy promoting several crucial steps of tumor progression, including the execution of the epithelial to mesenchymal transition (EMT) associated with enhancement in cell invasion, resistance to both anoikis and chemotherapeutic treatments. Recently it has been highlighted the central role of microRNAs (miRNAs) as regulators of tumor progression. Notably, in several tumors a strong deregulation of miRNAs is observed, supporting proliferation, invasion, and metabolic reprogramming of tumor cells. Here we demonstrated that cancer-associated fibroblasts induce a downregulation of miR-1247 in prostate cancer (PCa) cells. We proved that miR-1247 repression is functional for the achievement of EMT and increased cell invasion as well as stemness traits. These phenomena contribute to promote the metastatic potential of PCa cells as demonstrated by increased lung colonization in in vivo experiments. Moreover, as a consequence of miR-1247 downregulation, we observed a correlated increased expression level of neuropilin-1, a miR-1247 target involved as a coreceptor in the epidermal growth factor receptor signaling. Taken together, our data highlight miR-1247 as a potential target for molecular therapies aimed to block the progression and diffusion of PCa. |
| Databáze: | OpenAIRE |
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