Cell-autonomous and cell non-autonomous downregulation of tumor suppressor DAB2IP by microRNA-149-3p promotes aggressiveness of cancer cells
| Autor: | Roberta Bulla, Daniela Taverna, Arianna Bellazzo, Chiara Agostinis, Federica Tonon, Federica Serpi, Giulio Di Minin, Antonio Rosato, Gaia Zuccolotto, Isabella Monia Montagner, Elena Valentino, Licio Collavin, Cristina Zennaro, Daria Sicari, Miguel Mano, Denis Torre, Michael B. Stadler, Giannino Del Sal, Luigi Marchionni |
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| Přispěvatelé: | Bellazzo, Arianna, Di Minin, Giulio, Valentino, Elena, Sicari, Daria, Torre, Deni, Marchionni, Luigi, Serpi, Federica, Stadler, Michael B., Taverna, Daniela, Zuccolotto, Gaia, Montagner, Isabella Monia, Rosato, Antonio, Tonon, Federica, Zennaro, Cristina, Agostinis, Chiara, Bulla, Roberta, Mano, Miguel, Del Sal, Giannino, Collavin, Licio |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cancer microenvironment Stromal cell Biology Article Metastasis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation microRNA Human Umbilical Vein Endothelial Cells Tumor Microenvironment medicine Animals Humans RNA Neoplasm Molecular Biology Zebrafish Tumor microenvironment Cell Biology Cell growth Prostatic Neoplasms Cancer Hep G2 Cells HCT116 Cells medicine.disease tumor suppressor genes Neoplasm Proteins MicroRNAs 030104 developmental biology ras GTPase-Activating Proteins 030220 oncology & carcinogenesis PC-3 Cells Cancer cell Cancer research HeLa Cells Signal Transduction |
| Popis: | The tumor suppressor DAB2IP contributes to modulate the network of information established between cancer cells and tumor microenvironment. Epigenetic and post-transcriptional inactivation of this protein is commonly observed in multiple human malignancies, and can potentially favor progression of tumors driven by a variety of genetic mutations. Performing a high-throughput screening of a large collection of human microRNA mimics, we identified miR-149-3p as a negative post-transcriptional modulator of DAB2IP. By efficiently downregulating DAB2IP, this miRNA enhances cancer cell motility and invasiveness, facilitating activation of NF-kB signaling and promoting expression of pro-inflammatory and pro-angiogenic factors. In addition, we found that miR-149-3p secreted by prostate cancer cells induces DAB2IP downregulation in recipient vascular endothelial cells, stimulating their proliferation and motility, thus potentially remodeling the tumor microenvironment. Finally, we found that inhibition of endogenous miR-149-3p restores DAB2IP activity and efficiently reduces tumor growth and dissemination of malignant cells. These observations suggest that miR-149-3p can promote cancer progression via coordinated inhibition of DAB2IP in tumor cells and in stromal cells. |
| Databáze: | OpenAIRE |
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