ncRNA basic information ncRNA ID: MI0000084 ncRNA Database: miRBase ncRNA Name: miR-26b ncRNA Type: miRNA ncRNA Expression: up-regulated ncRNA Method: RT-PCR ncRNA Target Gene: ERBB2 ncRNA Pathway: NA Evidence (ncRNA-drug): validated

drug basic information Drug ID: DB00675 (APRD00123) Drug Name: Tamoxifen Drug Method: In the study, we reported that the ERBB2 expression is regulated at the post-transcriptional level by miR26a/b and the RNA-binding protein human antigen R (HuR), both of which associate with the 3-UTR of the ERBB2 transcripts. We demonstrated that miR26a/b inhibits the translation of ERBB2 mRNA, whereas HuR enhances the stability of the ERBB2 mRNA. In TAMR ER+ breast cancer cells with elevated ERBB2 expression, we observed a decrease in the level of miR26a/b and an increase in the level of HuR. The forced expression of miR26a/b or the depletion of HuR decreased ERBB2 expression in the TAMR cells, resulting in the reversal of tamoxifen resistance. In contrast, the inactivation of miR26a/b or forced expression of HuR decreased tamoxifen responsiveness of the parental ER+ breast cancer cells. We further showed that the increase in HuR expression in the TAMR ER+ breast cancer cells is attributable to an increase in the HuR mRNA isoform with shortened 3-UTR, which exhibits increased translational activity. This shortening of the HuR mRNA 3-UTR via alternative polyadenylation (APA) was observed to be dependent on cleavage stimulation factor subunit 2 (CSTF2/CstF-64), which is up-regulated in the TAMR breast cancer cells. Drug Response: sensitive

Cancer basic information Cancer: breast cancer Tissue/Cell: cell line (MCF7,T47D,MCF7/TAMR ,T47D/TAMR)

Other information Title: Post-transcriptional regulation of ERBB2 by miR26a/b and HuR confers resistance to tamoxifen in estrogen receptor-positive breast cancer cells. Journal: J Biol Chem Published: 2017 PubMed ID: 28637868