Abstract | PURPOSE: EXPERIMENTAL DESIGN: We performed microarray-based miRNA profiling of clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-141 both in vitro and in vivo, which was the most significantly downregulated in ccRCC tissues. RESULTS: A total of 74 miRNAs were dysregulated in ccRCC compared with normal tissues. miR-141 was remarkably downregulated in 92.6% (63/68) ccRCC tissues and would serve as a promising biomarker for discriminating ccRCC from normal tissues with an area under the receiver operating characteristics curve of 0.93. Overexpression of miR-141 robustly impaired ccRCC cell migratory and invasive properties and suppressed cell proliferation by arresting cells at G0-G1 phase in vitro and in human RCC orthotopic xenografts. Significantly, the antitumor activities of miR-141 were mediated by its reversal regulation of erythropoietin-producing hepatocellular (Eph) A2 (EphA2), which then relayed a signaling transduction cascade to attenuate the functions of focal adhesion kinase (FAK), AKT, and MMP2/9. In addition, a specific and inverse correlation between miR-141 and EphA2 expression was obtained in human ccRCC samples. Finally, miR-141 could be secreted from the ccRCC donor cells, and be taken up and function moderately in the ccRCC recipient cells. CONCLUSION: miR-141 serves as a potential biomarker for discriminating ccRCC from normal tissues and a crucial suppressor of ccRCC cell proliferation and metastasis by modulating the EphA2/p-FAK/p-AKT/ MMPs signaling cascade.
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Authors | Xuanyu Chen, Xuegang Wang, Anming Ruan, Weiwei Han, Yan Zhao, Xing Lu, Pei Xiao, Hangchuan Shi, Rong Wang, Li Chen, Shaoyong Chen, Quansheng Du, Hongmei Yang, Xiaoping Zhang |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 20
Issue 10
Pg. 2617-30
(May 15 2014)
ISSN: 1557-3265 [Electronic] United States |
PMID | 24647573
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | ©2014 American Association for Cancer Research. |
Chemical References |
- 3' Untranslated Regions
- MIRN141 microRNA, human
- MicroRNAs
- Receptor, EphA2
- Focal Adhesion Protein-Tyrosine Kinases
- Proto-Oncogene Proteins c-akt
- Matrix Metalloproteinases
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Topics |
- 3' Untranslated Regions
(genetics)
- Adult
- Aged
- Animals
- Carcinoma, Renal Cell
(genetics, metabolism, pathology)
- Cell Line, Tumor
- Cell Proliferation
- Female
- Focal Adhesion Protein-Tyrosine Kinases
(metabolism)
- Gene Expression Regulation, Neoplastic
- Humans
- Kidney Neoplasms
(genetics, metabolism, pathology)
- Male
- Matrix Metalloproteinases
(metabolism)
- Mice, Inbred BALB C
- Mice, Nude
- MicroRNAs
(genetics)
- Middle Aged
- Neoplasm Metastasis
- Oligonucleotide Array Sequence Analysis
- Proto-Oncogene Proteins c-akt
(metabolism)
- RNA Interference
- Receptor, EphA2
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Transplantation, Heterologous
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