論文 - 詳細
| RRC ID | 61281 |
|---|---|
| 著者 | Chen Y, Sun Y, Rao Q, Xu H, Li L, Chang C. |
| タイトル | Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status. |
| ジャーナル | Oncotarget |
| Abstract |
Mutational inactivation of the VHL tumor suppressor plays key roles in the development of renal cell carcinoma (RCC), and mutated VHL-mediated VEGF induction has become the main target for the current RCC therapy. Here we identified a signal pathway of VEGF induction by androgen receptor (AR)/miRNA-145 as a new target to suppress RCC progression. Mechanism dissection revealed that AR might function through binding to the androgen receptor element (ARE) located on the promoter region of miRNA-145 to suppress p53's ability to induce expression of miRNA-145 that normally suppresses expression of HIF2α/VEGF/MMP9/CCND1. Suppressing AR with AR-shRNA or introducing exogenous miRNA-145 mimic can attenuate RCC progression independent of VHL status. MiR-145 mimic in preclinical RCC orthotopic xenograft mouse model revealed its efficacy in suppression of RCC progression. These results together identified signals by AR-suppressed miRNA-145 as a key player in the RCC progression via regulating HIF2α/VEGF/MMP9/CCND1 expression levels. Blockade of the newly identified signal by AR inhibition or miRNA-145 mimics has promising therapeutic benefit to suppress RCC progression. |
| 巻・号 | 6(31) |
| ページ | 31203-15 |
| 公開日 | 2015-10-13 |
| DOI | 10.18632/oncotarget.4522 |
| PII | 4522 |
| PMID | 26304926 |
| PMC | PMC4741598 |
| MeSH | Animals Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism Binding Sites Carcinoma, Renal Cell / genetics Carcinoma, Renal Cell / metabolism* Carcinoma, Renal Cell / pathology Carcinoma, Renal Cell / therapy Cell Line, Tumor Cell Movement Cell Proliferation Cyclin D1 / genetics Cyclin D1 / metabolism Disease Progression Down-Regulation Gene Expression Regulation, Neoplastic Humans Kidney Neoplasms / genetics Kidney Neoplasms / metabolism* Kidney Neoplasms / pathology Kidney Neoplasms / therapy Male Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism Mice, Nude MicroRNAs / genetics MicroRNAs / metabolism* Mutation Neoplasm Invasiveness Promoter Regions, Genetic RNA Interference RNAi Therapeutics Receptors, Androgen / genetics Receptors, Androgen / metabolism* Signal Transduction Time Factors Transfection Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor A / metabolism Von Hippel-Lindau Tumor Suppressor Protein / genetics* Xenograft Model Antitumor Assays |
| IF | 5.168 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | OS-RC-2(RCB0735) |