Abstract |
Breast cancer is the most common type of cancer among women worldwide, and metastasis represents the most devastating stage of the disease. Recent studies have revealed that microRNAs ( miRNA) have critical roles to regulate cancer cell invasion and metastasis. Here we present evidence to show the role of miR-182 in breast cancer metastasis. miR-182 is upregulated in the malignant cell line variants of both human MCF10 and mouse 4T1 series. Ectopic expression of miR-182 enhanced breast cancer cell motility and invasiveness, whereas miR-182 inhibition resulted in opposite changes. In nude mice, miR-182 led to increased pulmonary colonization of cancer cells. We further demonstrated that miR-182 directly targets MIM (Missing in Metastasis), which suppresses metastasis by inhibiting ras homolog family member A (RhoA) activity and stress fiber formation in breast cancer cells. Restoring MIM expression completely blocked the pro- metastasis function of miR-182, while RhoA inhibition reversed the phenotypes of both miR-182 overexpression and MIM knockdown. In breast tumor samples, miR-182 induction is linked to downregulation of MIM, RhoA activation and poor prognosis. Hence, our data delineates the molecular pathway by which miR-182 promotes breast cancer invasion and metastasis, and may have important implication for the treatment of metastatic cancers.
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Authors | R Lei, J Tang, X Zhuang, R Deng, G Li, J Yu, Y Liang, J Xiao, H-Y Wang, Q Yang, G Hu |
Journal | Oncogene
(Oncogene)
Vol. 33
Issue 10
Pg. 1287-96
(Mar 06 2014)
ISSN: 1476-5594 [Electronic] England |
PMID | 23474751
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3' Untranslated Regions
- MTSS1 protein, human
- MicroRNAs
- Microfilament Proteins
- Mirn182 microRNA, human
- Neoplasm Proteins
- RHOA protein, human
- rhoA GTP-Binding Protein
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Topics |
- 3' Untranslated Regions
- Animals
- Binding Sites
- Breast Neoplasms
(genetics, metabolism, pathology)
- Cell Line, Tumor
- Cell Movement
- Disease-Free Survival
- Enzyme Activation
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Lung Neoplasms
(genetics, metabolism, secondary)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- MicroRNAs
(genetics)
- Microfilament Proteins
(genetics, metabolism)
- Neoplasm Invasiveness
- Neoplasm Proteins
(genetics, metabolism)
- Neoplasm Transplantation
- RNA Interference
- Stress Fibers
(metabolism)
- Tumor Burden
- rhoA GTP-Binding Protein
(metabolism)
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