MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1
Autor: | Yin-Yuan Mo, Mohit Sachdeva |
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Rok vydání: | 2009 |
Předmět: |
Cancer Research
Cell Blotting Western Fluorescent Antibody Technique Gene Expression Mice Nude Biology medicine.disease_cause Article Metastasis Mice RNA interference Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness MUC1 beta Catenin Cell growth Cadherin Reverse Transcriptase Polymerase Chain Reaction Mucin-1 medicine.disease Cadherins Molecular biology Immunohistochemistry Metastasis Gene Gene Expression Regulation Neoplastic MicroRNAs medicine.anatomical_structure Oncology Tissue Array Analysis Cancer research Carcinogenesis |
Zdroj: | Cancer research. 70(1) |
ISSN: | 1538-7445 |
Popis: | MicroRNAs are important gene regulators that could play a profound role in tumorigenesis. Our previous studies indicate that miR-145 is a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that miR-145 exerts its function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells; in contrast, the antisense oligo against miR-145 increases cell invasion. miR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145–mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with Western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β-catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth but also cell invasion and metastasis. Cancer Res; 70(1); 378–87 |
Databáze: | OpenAIRE |
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