Dataset Information


CCAR1 5' UTR as a natural miRancer of miR-1254 overrides tamoxifen resistance.

ABSTRACT: MicroRNAs (miRNAs) typically bind to unstructured miRNA-binding sites in target RNAs, leading to a mutual repression of expression. Here, we report that miR-1254 interacts with structured elements in cell cycle and apoptosis regulator 1 (CCAR1) 5' untranslated region (UTR) and this interaction enhances the stability of both molecules. miR-1254 can also act as a repressor when binding to unstructured sites in its targets. Interestingly, structured miR-1254-targeting sites act as both a functional RNA motif-sensing unit, and an independent RNA functional unit that enhances miR-1254 expression. Artificially designed miRNA enhancers, termed "miRancers", can stabilize and enhance the activity of miRNAs of interest. We further demonstrate that CCAR1 5' UTR as a natural miRancer of endogenous miR-1254 re-sensitizes tamoxifen-resistant breast cancer cells to tamoxifen. Thus, our study presents a novel model of miRNA function, wherein highly structured miRancer-like motif-containing RNA fragments or miRancer molecules specifically interact with miRNAs, leading to reciprocal stabilization.


PROVIDER: S-EPMC4897177 | BioStudies | 2016-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5549757 | BioStudies
1000-01-01 | S-EPMC6181905 | BioStudies
2021-01-01 | S-EPMC7907678 | BioStudies
2016-01-01 | S-EPMC4822641 | BioStudies
1000-01-01 | S-EPMC5548864 | BioStudies
2017-01-01 | S-EPMC6179579 | BioStudies
1000-01-01 | S-EPMC4284514 | BioStudies
2017-01-01 | S-EPMC6188638 | BioStudies
2019-01-01 | S-EPMC6603045 | BioStudies
2010-01-01 | S-EPMC2903801 | BioStudies