Unknown

Dataset Information

0

Mechanisms of the androgen receptor splicing in prostate cancer cells.


ABSTRACT: Prostate tumors develop resistance to androgen deprivation therapy (ADT) by multiple mechanisms, one of which is to express constitutively active androgen receptor (AR) splice variants lacking the ligand-binding domain. AR splice variant 7 (AR-V7, also termed AR3) is the most abundantly expressed variant that drives prostate tumor progression under ADT conditions. However, the molecular mechanism by which AR-V7 is generated remains unclear. In this manuscript, we demonstrated that RNA splicing of AR-V7 in response to ADT was closely associated with AR gene transcription initiation and elongation rates. Enhanced AR gene transcription by ADT provides a prerequisite condition that further increases the interactions between AR pre-mRNA and splicing factors. Under ADT conditions, recruitment of several RNA splicing factors to the 3' splicing site for AR-V7 was increased. We identified two RNA splicing enhancers and their binding proteins (U2AF65 and ASF/SF2) that had critical roles in splicing AR pre-mRNA into AR-V7. These data indicate that ADT-induced AR gene transcription rate and splicing factor recruitment to AR pre-mRNA contribute to the enhanced AR-V7 levels in prostate cancer cells.

PROVIDER: S-EPMC4553036 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC4941255 | BioStudies
| S-EPMC4270852 | BioStudies
| S-EPMC3517715 | BioStudies
| S-EPMC4215833 | BioStudies
| S-EPMC3894334 | BioStudies
| S-EPMC6788855 | BioStudies
2010-01-01 | S-EPMC2947883 | BioStudies
| S-EPMC8913362 | BioStudies
| S-EPMC7201592 | BioStudies
| S-EPMC3337879 | BioStudies