Rane, Jayant K, Erb, Holger Hh, Nappo, Giovanna et al. (5 more authors) (2016) Inhibition of the glucocorticoid receptor results in an enhanced miR-99a/100-mediated radiation response in stem-like cells from human prostate cancers. Oncotarget. ISSN 1949-2553
Abstract
Radiation therapy is a major primary treatment option for both localized early stage prostate cancer, and for advanced, regionally un-resectable, cancer. However, around 30% of patients still experience biochemical recurrence after radiation therapy within 10 years. Thus, identification of better biomarkers and new targets are urgently required to improve current therapeutic strategies. The miR-99 family has been shown to play an important role in the regulation of the DNA damage response, via targeting of the SWI/SNF chromatin remodeling factors, SMARCA5 and SMARCD1 in cell line models. In the present study, we have demonstrated that low expression of miR-99a and miR-100 is present in cell populations which are relatively radiation insensitive, for example in prostate cancer stem cells and in castration-resistant prostate cancer. Additionally, treatment of cells with the synthetic glucocorticoid, Dexamethasone resulted in decreased miR-99a and 100 expression, suggesting a new mechanism of miR-99a and 100 regulation in androgen-independent prostate cells. Strikingly, treatment of prostate cells with the glucocorticoid receptor inhibitor, Mifepristone was found to sensitize prostate cells to radiation by increasing the levels of miR-99a and miR-100. These results qualify the miR99 family as markers of radiation sensitivity and as potential therapeutic targets to improve efficiency of radiotherapy.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Dates: |
|
Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Biology (York) > Yorkshire Cancer Research Unit (York) |
Depositing User: | Pure (York) |
Date Deposited: | 04 Jul 2016 13:55 |
Last Modified: | 05 Dec 2024 00:13 |
Published Version: | https://doi.org/10.18632/oncotarget.10207 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.18632/oncotarget.10207 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101878 |
Downloads
Filename: Maitland_20160718_manuscript_final_version.pdf
Description: Maitland 20160718_manuscript_AAM