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NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs

Tyler Sheetz1,2,3, Joseph Mills1,2, Anna Tessari1,2

  • 1Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

Cancers
|July 16, 2020
PubMed

Insights

Targeting the nucleolin (NCL) protein, overexpressed in prostate cancer (PCa), reduced tumor cell proliferation and migration. This suggests NCL as a potential therapeutic target for advanced-stage PCa, including castration-resistant forms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Prostate cancer (PCa) is a leading cause of cancer death in men, often progressing to castration-resistant prostate cancer (CRPC) despite androgen deprivation therapy (ADT).
  • Nucleolin (NCL), a protein overexpressed and cell surface-localized in various tumors, presents a potential therapeutic target.
  • Previous studies identified an anti-NCL single-chain fragment variable (scFv) with anti-cancer activity in breast cancer.

Purpose of the Study:

  • To investigate nucleolin (NCL) as a therapeutic target for prostate cancer (PCa), including castration-resistant forms (CRPC).
  • To evaluate the efficacy of an anti-NCL scFv in inhibiting PCa cell proliferation and migration.

Main Methods:

  • Analysis of public databases for NCL mRNA levels in relation to PCa Gleason Scores and tumor stage.
  • Utilizing anti-NCL scFv to assess NCL surface expression on DU145, PC3 (CRPC), and LNCaP (androgen-sensitive) cell lines.
  • Measuring the impact of NCL inhibition on PCa cell proliferation, migration, and oncogenic microRNA biogenesis.

Main Results:

  • Higher NCL mRNA levels correlated with higher Gleason Scores and advanced/metastatic PCa.
  • NCL was confirmed to be expressed on the surface of all tested PCa cell lines.
  • Targeting NCL with scFv significantly reduced PCa cell proliferation and migration, with context-dependent effects on microRNA biogenesis.

Conclusions:

  • Nucleolin (NCL) is a valid therapeutic target for prostate cancer (PCa), including advanced and castration-resistant stages.
  • NCL inhibition effectively reduces key hallmarks of malignancy in PCa cells.
  • Targeting NCL offers a potential novel therapeutic strategy for patients with advanced-stage PCa.
Keywords:
castration-resistant prostate cancermicroRNAsnucleolinprostate cancer

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