Related Experiment Video

Updated: Mar 19, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
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An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

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MiR-4638-5p inhibits castration resistance of prostate cancer through repressing Kidins220 expression and PI3K/AKT

Yang Wang1,2, Ning Shao1,2, Xueying Mao3

  • 1Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.

Oncotarget
|June 23, 2016
PubMed

Insights

MicroRNA miR-4638-5p is underexpressed in castration-resistant prostate cancer (CRPC). Its loss promotes CRPC growth via Kidins220 and the PI3K/AKT pathway, offering potential therapeutic targets.

Area of Science:

  • Molecular Oncology
  • Cancer Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are crucial regulators in prostate cancer progression.
  • Castration-resistant prostate cancer (CRPC) remains a significant clinical challenge.
  • Identifying molecular drivers of CRPC is essential for developing new therapies.

Purpose of the Study:

  • To identify microRNAs associated with the development of castration resistance in prostate cancer.
  • To elucidate the functional role of miR-4638-5p in prostate cancer progression.
  • To investigate the downstream targets and pathways regulated by miR-4638-5p.

Main Methods:

  • MicroRNA microarray analysis comparing CRPC and androgen-dependent prostate cancer (ADPC) samples.
  • Quantitative PCR (qPCR) for miRNA expression validation.
  • In vitro and in vivo functional assays to assess miR-4638-5p's role.
  • Target gene identification and pathway analysis (e.g., Kidins220, PI3K/AKT, VEGF).

Main Results:

  • miR-4638-5p was commonly underexpressed in CRPC compared to ADPC.
  • Restoration of miR-4638-5p inhibited androgen-independent growth of prostate cancer cells.
  • Kidins220 was identified as a direct target of miR-4638-5p, and its knockdown mimicked miR-4638-5p restoration.
  • Kidins220 activates the PI3K/AKT pathway, crucial for CRPC.
  • miR-4638-5p regulates angiogenesis via Kidins220, VEGF, and the PI3K/AKT pathway.

Conclusions:

  • Downregulation of miR-4638-5p contributes to CRPC development and progression.
  • The miR-4638-5p/Kidins220/PI3K/AKT axis is a key pathway in CRPC.
  • miR-4638-5p influences angiogenesis, impacting prostate cancer progression.
  • miR-4638-5p and its downstream effectors represent potential biomarkers and therapeutic targets for CRPC.
Keywords:
Kidins220PI3K/AKT pathwayangiogenesiscastration resistant prostate cancermiR-4638-5p

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