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Androgen receptor regulates SRC expression through microRNA-203

Man Kit Siu1,2,3, Wei-Yu Chen4,5, Hong-Yuan Tsai2

  • 1Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.

Oncotarget
|March 31, 2016
PubMed

Insights

High SRC kinase levels correlate with low androgen receptor (AR) activity in prostate cancer (PCa). Activated AR induces miR-203, which suppresses SRC, suggesting a pathway to control PCa metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • SRC kinase is crucial in development and tumor progression.
  • An inverse relationship exists between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa).
  • The specific mechanisms of AR/SRC crosstalk in metastatic PCa remain unclear.

Purpose of the Study:

  • To investigate the relationship between AR, SRC, and microRNA-203 (miR-203) in prostate cancer progression.
  • To elucidate the role of miR-203 in regulating SRC expression and its impact on AR signaling.
  • To determine the clinical relevance of the AR-miR-203-SRC axis in metastatic PCa.

Main Methods:

  • Analysis of SRC levels and AR gene signatures in patient data.
  • In vitro studies using PCa model systems to examine AR activation, miR-203 induction, and SRC regulation.
  • Luciferase assays to confirm direct binding of miR-203 to SRC 3' UTR.
  • Validation of findings in clinical datasets and patient specimens.

Main Results:

  • Patients with high SRC levels showed reduced canonical AR gene signatures.
  • Activated AR induced miR-203, leading to decreased SRC levels in PCa models.
  • miR-203 directly targets SRC mRNA, regulating its stability upon AR activation.
  • Prostate cancer cell migration and growth correlated with decreased miR-203 and increased SRC.

Conclusions:

  • SRC induction promotes PCa metastasis by disrupting AR signaling via miR-203 inactivation.
  • The AR-miR-203-SRC axis represents a critical regulatory pathway in prostate cancer.
  • Targeting this pathway may offer therapeutic strategies for metastatic PCa.
Keywords:
SRCandrogen receptor (AR)microRNA (miR)-203prostate cancer (PCa)

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