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

Journal article

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.

Authors: Ray, J; Haughey, C; Hoey, C; Jeon, J; Murphy, R

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Cancer Letters
• Volume: 473
• Pages: 107-117
• Publication date: 2019-12-23
• Acceptance date: 2019-12-19
• DOI: 10.1016/j.canlet.2019.12.025
• EISSN: 1872-7980
• ISSN: 0304-3835
• Pmid: 31874245
• Language: English
• Keywords: RXRA; radiation resistance; microRNA-191; microRNA; primary prostate cancer