| 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
|
| リソース情報 |
| ヒト・動物細胞 |
OS-RC-2(RCB0735) |
