Related Experiment Video

Updated: Jun 29, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

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m6A Modification Promotes EMT and Metastasis of Castration-Resistant Prostate Cancer by Upregulating NFIB

Feng Shu1, Hao Liu2, Xiaohui Chen1

  • 1Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China.

Cancer Research
|March 27, 2024
PubMed

Insights

Nuclear factor I/B (NFIB) drives metastasis in androgen receptor-negative castration-resistant prostate cancer (CRPC) by promoting epithelial-to-mesenchymal transition (EMT). Targeting the N6-methyladenosine (m6A)/NFIB pathway offers a new strategy for CRPC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Androgen receptor (AR)-negative castration-resistant prostate cancer (CRPC) presents a significant clinical challenge due to limited treatment options.
  • Understanding the molecular drivers of AR-negative CRPC is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of nuclear factor I/B (NFIB) in AR-negative CRPC progression and metastasis.
  • To elucidate the regulatory mechanisms, including N6-methyladenosine (m6A) modification, involved in NFIB upregulation in AR-negative CRPC.

Main Methods:

  • Analysis of NFIB expression in patient-derived AR-negative CRPC tumors and cell lines.
  • Assessment of NFIB's impact on epithelial-to-mesenchymal transition (EMT) and cell migration.
  • Investigation of NFIB's direct transcriptional targets involved in EMT.
  • In vivo metastasis models.
  • Analysis of m6A modification on NFIB and TRIM8 mRNA.

Main Results:

  • NFIB was upregulated in AR-negative CRPC and associated with an EMT phenotype.
  • NFIB loss inhibited EMT and CRPC cell migration, with NFIB directly regulating E-cadherin and vimentin.
  • In vivo studies confirmed NFIB's role in metastasis.
  • N6-methyladenosine (m6A) modification upregulated NFIB in AR-negative CRPC by increasing mRNA stability via YTHDF2.
  • ALKBH5 downregulation increased m6A modification of TRIM8 mRNA, enhancing NFIB protein stability.

Conclusions:

  • Upregulation of NFIB, driven by m6A modification, promotes EMT and metastasis in AR-negative CRPC.
  • The m6A/NFIB axis represents a potential therapeutic target for preventing and treating AR-negative CRPC metastasis.

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