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Updated: May 28, 2025

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
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miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Published on: September 8, 2015

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Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 (IGF2BP2) Promotes Castration-Resistant Prostate Cancer

Taruna Saini1, Devesh Srivastava1, Rajnikant Raut1

  • 1Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, India.

Cancer Reports (Hoboken, N.J.)
|February 13, 2025
PubMed
Abstract

Insights

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) promotes castration-resistant prostate cancer (CRPC) by stabilizing androgen receptor variant 7 (AR-V7) mRNA. Targeting IGF2BP2 may offer a new therapeutic strategy for CRPC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Castration-resistant prostate cancer (CRPC) is challenging to treat due to the emergence of androgen receptor variant 7 (AR-V7).
  • AR-V7 lacks the ligand-binding domain, rendering it resistant to standard androgen-deprivation therapies.
  • The mechanisms regulating AR-V7 expression and function in CRPC are not fully understood.

Purpose of the Study:

  • To investigate the role of IGF2BP2 in regulating AR-V7 expression and CRPC progression.
  • To explore IGF2BP2 as a potential therapeutic target for CRPC.

Main Methods:

  • Analysis of clinical mRNA expression data from CRPC patients.
  • In vitro experiments involving IGF2BP2 knockdown and overexpression in CRPC cells.
  • Assays included qRT-PCR, immunoblot, colony-formation, MTT, RIP-qPCR, and actinomycin-D treatment.
  • Domain-deletion analysis of IGF2BP2 was performed.

Main Results:

  • IGF2BP2 is upregulated in CRPC and correlates with higher Gleason scores.
  • IGF2BP2 silencing downregulates AR-V7 and its targets, increasing sensitivity to enzalutamide.
  • IGF2BP2 overexpression enhances AR-V7 expression and confers enzalutamide resistance.
  • IGF2BP2 binds to the AR-V7 intronic splicing enhancer, stabilizing its mRNA.

Conclusions:

  • IGF2BP2 is a key regulator of AR-V7 expression and stability in CRPC.
  • IGF2BP2 represents a novel therapeutic target for CRPC treatment.
  • Targeting IGF2BP2 could overcome resistance to enzalutamide in prostate cancer.
Keywords:
AR‐V7IGF2BP2RNA‐binding proteinsandrogen receptorcastration‐resistant prostate cancer

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