ncRNA basic information
ncRNA ID:
MI0000083/MI0000750
ncRNA Database:
miRBase
ncRNA Name:
miR-26a
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