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

Jessica Ray, Charles Haughey, Christianne Hoey, Jouhyun Jeon, Ross Murphy, Lara Dura-Perez, Nuala McCabe, Michelle Downes, Suneil Jain, Paul C Boutros, Ian G Mills, Stanley K Liu

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)107-117
Number of pages11
JournalCancer Letters
Publication statusPublished (in print/issue) - 31 Mar 2020

Bibliographical note

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.


  • Alitretinoin/administration & dosage
  • Animals
  • Antineoplastic Agents/administration & dosage
  • Biomarkers, Tumor/metabolism
  • Cell Line, Tumor
  • Chemoradiotherapy, Adjuvant/methods
  • Disease-Free Survival
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic/drug effects
  • Gene Knockdown Techniques
  • Humans
  • Kallikreins/blood
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • MicroRNAs/agonists
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local/blood
  • Primary Cell Culture
  • Prognosis
  • Prostate/pathology
  • Prostate-Specific Antigen/blood
  • Prostatectomy
  • Prostatic Neoplasms/blood
  • Radiation Tolerance/drug effects
  • Retinoid X Receptor alpha/agonists
  • Survival Rate
  • Time Factors
  • Xenograft Model Antitumor Assays


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