MiR-33a suppresses breast cancer cell proliferation and metastasis by targeting ADAM9 and ROS1

• Published in: Protein & cell 2015-12, Vol.6 (12), p.881-889
• Main Authors: Zhang, Chuankai, Zhang, Yunda, Ding, Weiji, Lin, Yancheng, Huang, Zhengjie, Luo, Qi
• Format: Article
• Language: English
• Subjects: ADAM Proteins - deficiency; ADAM Proteins - genetics; Animals; Biochemistry; Biomedical and Life Sciences; breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Biology; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Developmental Biology; Female; Human Genetics; Humans; Life Sciences; Lung Neoplasms - secondary; Membrane Proteins - deficiency; Membrane Proteins - genetics; metastasis; Mice; MicroRNAs - genetics; Middle Aged; miR-33a; miRNAs; Neoplasm Invasiveness; Neoplasm Metastasis; proliferation; Protein Science; Protein-Tyrosine Kinases - deficiency; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - deficiency; Proto-Oncogene Proteins - genetics; Research Article; Stem Cells; 乳腺上皮细胞; 乳腺癌细胞; 体外增殖; 动脉粥样硬化; 抑制肿瘤; 细胞增殖; 非编码RNA
• ISSN: 1674-800X; 1674-8018
• DOI: 10.1007/s13238-015-0223-8

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 repotted to play an important role in lipid homeostasis, atherosclerosis, and hepatic fibrosis, the functions of miR-33a in tumor progression and metastasis are lar- gely 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.