ncRNA basic information ncRNA ID: MI0000299 ncRNA Database: miRBase ncRNA Name: miR-222 ncRNA Type: miRNA ncRNA Expression: up-regulated ncRNA Method: RT-PCR ncRNA Target Gene: NA ncRNA Pathway: NA Evidence (ncRNA-drug): validated

drug basic information Drug ID: DB00675 (APRD00123) Drug Name: Tamoxifen Drug Method: miRNA microarray analysis of MCF-7 cell lines that are either sensitive (parental) or resistant (4-hydroxytamoxifen-resistant (OHTR)) to tamoxifen showed significant (>1.8-fold) up-regulation of eight miRNAs and marked down-regulation (>50%) of seven miRNAs in OHTR cells compared with parental MCF-7 cells. Increased expression of three of the most promising up-regulated (miR-221, miR-222, and miR-181) and down-regulated (miR-21, miR-342, and miR-489) miRNAs was validated by real-time reverse transcription-PCR. The expression of miR-221 and miR-222 was also significantly (2-fold) elevated in HER2/neu-positive primary human breast cancer tissues that are known to be resistant to endocrine therapy compared with HER2/neu-negative tissue samples. Ectopic expression of miR-221/222 rendered the parental MCF-7 cells resistant to tamoxifen. The protein level of the cell cycle inhibitor p27Kip1, a known target of miR-221/222, was reduced by 50% in OHTR cells and by 28-50% in miR-221/222-overexpressing MCF-7 cells. Furthermore, overexpression of p27Kip1 in the resistant OHTR cells caused enhanced cell death when exposed to tamoxifen. Drug Response: resistant

Cancer basic information Cancer: breast cancer Tissue/Cell: cell line (MCF-7,OHTR)

Other information Title: MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. Journal: J Biol Chem Published: 2008 PubMed ID: 18708351