ncRNA basic information
ncRNA ID:
MI0000783
ncRNA Database:
miRBase
ncRNA Name:
miR-375
ncRNA Type:
miRNA
ncRNA Expression:
down-regulated
ncRNA Method:
qRT-PCR
ncRNA Target Gene:
MTDH
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00675 (APRD00123)
Drug Name:
Tamoxifen
Drug Method:
To investigate the role of miRNAs in the development of resistance to tamoxifen as well as accompanying EMT-like properties, we established a tamoxifen-resistant (TamR) model by continually exposing MCF-7 breast cancer cells to tamoxifen. In addition to the molecular changes known to be involved in acquired tamoxifen resistance, TamR cells displayed mesenchymal features and had increased invasiveness. Genome-wide miRNA microarray analysis revealed that miRNA-375 was among the top downregulated miRNAs in resistant cells. Re-expression of miR-375 was sufficient to sensitize TamR cells to tamoxifen and partly reversed EMT. A combination of mRNA profiling, bioinformatics analysis and experimental validation identified metadherin (MTDH) as a direct target of miR-375. Knockdown of MTDH partially phenocopied the effects of miR-375 on the sensitivity to tamoxifen and the reversal of EMT. We observed an inverse correlation between the expression of miR-375 and its target MTDH in primary breast cancer samples, implying the pathological relevance of targeting. Finally, tamoxifen-treated patients with higher expression of MTDH had a shorter disease-free survival and higher risk of relapse.
Drug Response:
resistant
Cancer basic information
Cancer:
breast cancer
Tissue/Cell:
cell line (MCF-7, MDA-MB-231, H1703, H1299,HEK-293FT,Ovcar-5)
Other information
Title:
Re-expression of microRNA-375 reverses both tamoxifen resistance and accompanying EMT-like properties in breast cancer.
Journal:
Oncogene
Published:
2013
PubMed ID:
22508479