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Updated: May 1, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1
1Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois 62794, USA.
Abstract:
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 beta-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 beta-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.
Insights
MicroRNA-145 (miR-145) acts as a tumor suppressor by inhibiting cell growth and invasion. It targets MUC1, reducing metastasis and impacting key cancer-related pathways.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are crucial gene regulators implicated in tumorigenesis.
- Previous research identified miR-145 as a tumor suppressor inhibiting cancer cell growth.
- The precise mechanisms and cell-specific functions of miR-145 in metastasis require further elucidation.
Purpose of the Study:
- To investigate the cell-specific role of miR-145 in cancer progression.
- To identify the molecular targets of miR-145 involved in cell invasion and metastasis.
- To elucidate the downstream signaling pathways affected by miR-145-mediated MUC1 regulation.
Main Methods:
- Cell growth and invasion assays in various cancer cell lines (MCF-7, HCT-116, metastatic breast cancer lines).
- Experimental metastasis animal model to assess in vivo tumor spread.
- Luciferase reporter assays, Western blotting, and immunofluorescence staining to validate MUC1 as a direct miR-145 target.
- RNA interference (RNAi) to mimic miR-145 function.
Main Results:
- miR-145 inhibited cell growth in MCF-7 and HCT-116 cells but not in metastatic breast cancer lines.
- miR-145 significantly suppressed cell invasion and lung metastasis in vivo.
- MUC1 was identified as a direct target of miR-145, and its suppression by miR-145 reduced cell invasion.
- miR-145-mediated MUC1 suppression led to decreased beta-catenin and cadherin 11 levels.
Conclusions:
- miR-145 functions as a tumor suppressor by inhibiting both cancer cell growth and invasion.
- The miR-145/MUC1 axis plays a critical role in controlling cancer cell invasion and metastasis.
- Targeting miR-145 or its downstream effectors may offer therapeutic strategies for reducing cancer spread.
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