Androgen receptor regulates SRC expression through microRNA-203

Man Kit Siu, Wei Yu Chen, Hong Yuan Tsai, Hsiu Lien Yeh, Juan Juan Yin, Shih Yang Liu, Yen-Nien Liu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The SRC kinase has pivotal roles in multiple developmental processes and in tumor progression. An inverse relationship has been observed between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the modulation of AR/SRC crosstalk that leads to metastatic PCa is unclear. Here, we showed that patients with high SRC levels displayed correspondingly low canonical AR gene signatures. Our results demonstrated that activated AR induced miR-203 and reduced SRC levels in PCa model systems. miR-203 directly binds to the 3' UTR of SRC and regulates the stability of SRC mRNA upon AR activation. Moreover, we found that progressive PCa cell migration and growth were associated with a decrease in AR-regulated miR-203 and an increase in SRC. Relationships among AR, miR-203, and SRC were also confirmed in clinical datasets and specimens. We suggest that the induction of SRC results in increased PCa metastasis that is linked to the dysregulation of the AR signaling pathway through the inactivation of miR-203.

Original languageEnglish
Pages (from-to)25726-25741
Number of pages16
JournalOncotarget
Volume7
Issue number18
DOIs
Publication statusPublished - May 1 2016

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Keywords

  • Androgen receptor (AR)
  • MicroRNA (miR)-203
  • Prostate cancer (PCa)
  • SRC

ASJC Scopus subject areas

  • Oncology

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