Abstract |
MicroRNAs ( miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression by sequence-specifically targeting multiple mRNAs. Although miR-33a was recently reported to play an important role in lipid homeostasis, atherosclerosis, and hepatic fibrosis, the functions of miR-33a in tumor progression and metastasis are largely unknown. Here, we found that downregulated miR-33a in breast cancer tissues correlates with lymph node metastasis. MiR-33a expression is significantly lower in the highly metastatic breast cancer cell lines than the noncancerous breast epithelial cells and non-metastatic breast cancer cells. Moreover, the overexpression of miR-33a in metastatic breast cancer cells remarkably decreases cell proliferation and invasion in vitro and significantly inhibits tumor growth and lung metastasis in vivo, whereas its knockdown in non-metastatic breast cancer cells significantly enhances cell proliferation and invasion in vitro and promotes tumor growth and lung metastasis in vivo. Combining bioinformatics prediction and biochemical analyses, we showed that ADAM9 and ROS1 are direct downstream targets of miR-33a. These findings identified miR-33a as a negative regulator of breast cancer cell proliferation and metastasis.
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Authors | Chuankai Zhang, Yunda Zhang, Weiji Ding, Yancheng Lin, Zhengjie Huang, Qi Luo |
Journal | Protein & cell
(Protein Cell)
Vol. 6
Issue 12
Pg. 881-9
(Dec 2015)
ISSN: 1674-8018 [Electronic] Germany |
PMID | 26507842
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- MIRN33a microRNA, human
- Membrane Proteins
- MicroRNAs
- Proto-Oncogene Proteins
- Protein-Tyrosine Kinases
- ROS1 protein, human
- ADAM Proteins
- ADAM9 protein, human
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Topics |
- ADAM Proteins
(deficiency, genetics)
- Animals
- Breast Neoplasms
(genetics, pathology)
- Cell Line, Tumor
- Cell Movement
(genetics)
- Cell Proliferation
(genetics)
- Female
- Humans
- Lung Neoplasms
(secondary)
- Membrane Proteins
(deficiency, genetics)
- Mice
- MicroRNAs
(genetics)
- Middle Aged
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Protein-Tyrosine Kinases
(deficiency, genetics)
- Proto-Oncogene Proteins
(deficiency, genetics)
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