MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1.

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.

• Authors: Mohit Sachdeva, Yin-Yuan Mo
• Journal: Cancer research (Cancer Res) Vol. 70 Issue 1 Pg. 378-87 (Jan 01 2010) ISSN: 1538-7445 [Electronic] United States
• PMID: 19996288 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cadherins
• MIRN145 microRNA, human
• MicroRNAs
• Mucin-1
• beta Catenin
• osteoblast cadherin

Topics

• Animals
• Blotting, Western
• Cadherins (biosynthesis)
• Cell Line, Tumor
• Fluorescent Antibody Technique
• Gene Expression
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Mucin-1 (genetics, metabolism)
• Neoplasm Invasiveness (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Tissue Array Analysis
• beta Catenin (biosynthesis)