Abstract | BACKGROUND: METHODS: In situ hybridization was used to detect miR-133a expression in formalin-fixed paraffin-embedded breast surgical specimens from 26 benign, 34 pericancerously normal and 90 cancerous tissues. qRT-PCR was performed to assess miR-133a levels in 6 breast cell lines and 10 benign and 18 cancerous fresh breast tissue specimens. Cell viability, migration, and invasion assays were used to determine the role of miR-133a in regulation of breast cancer cell growth, migration, and invasion, respectively. Luciferase assay was performed to assess miR-133a binding to FSCN1 gene. RESULTS: Expression of miR-133a was reduced from normal through benign to cancerous breast tissues. Expression of miR-133a was also low in breast cancer cell lines. The reduced miR-133a expression was associated with lymph nodes metastasis, high clinical stages, and shorter relapse-free survivals of patients with breast cancer. Furthermore, transfection of miR-133a oligonucleotides slightly inhibited growth but significantly decreased migration and invasion capacity of breast cancer cells, compared with negative controls, whereas knockdown of miR-133a expression induced breast cancer cell migration and invasion. In addition, we identified a putative miR-133a binding site in the 3'-untranslated region (UTR) of Fascin1 (FSCN1) gene using an online bioinformatical tool. We found that miR-133a transfection significantly reduced expression of FSCN1 mRNA and protein. The luciferase reporter assay confirmed that FSCN1 was the direct target gene of miR-133a. CONCLUSIONS: miR-133a expression was lost in breast cancer tissues, loss of which was associated with lymph nodes metastasis, high clinical stages and shorter relapse-free survivals of patients with breast cancer. Functionally, miR-133a can suppress tumor cell invasion and migration and targeted the expression of FSCN1. Future study will verify whether detection of miR-133a expression can served as a novel biomarker for breast cancer progression and patient prognosis.
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Authors | Zheng-sheng Wu, Chao-qun Wang, Ru Xiang, Xue Liu, Shan Ye, Xue-qing Yang, Gui-hong Zhang, Xiao-chun Xu, Tao Zhu, Qiang Wu |
Journal | BMC cancer
(BMC Cancer)
Vol. 12
Pg. 51
(Feb 01 2012)
ISSN: 1471-2407 [Electronic] England |
PMID | 22292984
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- MIRN133 microRNA, human
- MicroRNAs
- Neoplasm Proteins
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Topics |
- Blotting, Western
- Breast Neoplasms
(genetics, metabolism, mortality, pathology)
- Carcinoma
(genetics, metabolism, mortality, pathology)
- Cell Line, Tumor
- Cell Movement
(physiology)
- Cell Proliferation
- Cell Survival
- Cohort Studies
- Female
- Humans
- MicroRNAs
(metabolism)
- Neoplasm Invasiveness
(genetics)
- Neoplasm Proteins
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Survival Analysis
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