miR-191 promotes radiation resistance of prostate cancer through interaction with RXRA - ScienceDirect

miR-191 promotes radiation resistance of prostate cancer through interaction with RXRA - ScienceDirect:

sciencedirect.com

miR-191 promotes radiation resistance of prostate cancer through interaction with RXRA

46-58 minutes
Under a Creative Commons license
open access

Highlights

•miR-191 expression is elevated in prostate cancer patients with higher Gleason score.
•High miR-191 promotes radiation survival and targets retinoid X receptor alpha, RXRA.
•Treatment with the RXRA agonist 9-cis-retinoic acid restores radiosensitivity.
•Patients with high miR-191 and low RXRA experienced quicker biochemical recurrence.

Abstract

Radiation therapy is a common treatment for prostate cancer, however recurrence remains a problem. MicroRNA expression is altered in prostate cancer and may promote therapy resistance. Through bioinformatic analyses of TCGA and CPC-GENE patient cohorts, we identified higher miR-191 expression in tumor versus normal tissue, and increased expression in higher Gleason scores. In vitro and in vivo experiments demonstrated that miR-191 overexpression promotes radiation survival, and contributes to a more aggressive phenotype. Retinoid X receptor alpha, RXRA, was discovered to be a novel target of miR-191, and knockdown recapitulated radioresistance. Furthermore, treatment of prostate cancer cells with the RXRA agonist 9-cis-retinoic acid restored radiosensitivity. Supporting this relationship, patients with high miR-191 and low RXRA abundance experienced quicker biochemical recurrence. Reduced RXRA translated to a higher risk of distant failure after radiotherapy. Notably, this miR-191/RXRA interaction was conserved in a novel primary cell line derived from radiorecurrent prostate cancer. Together, our findings demonstrate that miR-191 promotes prostate cancer survival after radiotherapy, and highlights retinoids as a potential option to improve radiotherapy response.

Keywords

microRNA
microRNA-191
RXRA
radiation resistance
primary prostate cancer

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