In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation

Flavia Pichiorri1, Dario Palmieri, Luciana De Luca

  • 1Division of Hematology, College of Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. flavia.pichiorri@osumc.edu

Insights

Nucleolin (NCL) regulates microRNAs (miRNAs) crucial for breast cancer. Targeting NCL with aptamers reduces these miRNAs, inhibiting cancer cell aggressiveness and offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) play a significant role in human cancers, but therapeutic modulation of their levels remains challenging.
  • Nucleolin (NCL), a key nucleolar protein, has been implicated in various cellular processes.

Purpose of the Study:

  • To investigate the role of nucleolin (NCL) in regulating microRNA (miRNA) expression in breast cancer.
  • To explore the therapeutic potential of targeting NCL for breast cancer treatment.

Main Methods:

  • Analysis of NCL's posttranscriptional regulation of specific miRNAs (miR-21, miR-221, miR-222, miR-103) involved in breast cancer.
  • Assessment of NCL and NCL-dependent miRNA expression in human breast tumors.
  • Inhibition of NCL using guanosine-rich aptamers in vitro and in vivo models.

Main Results:

  • NCL was found to posttranscriptionally regulate key breast cancer-associated miRNAs.
  • NCL is overexpressed in breast tumors, correlating with NCL-dependent miRNA levels.
  • NCL inhibition via aptamers decreased NCL-dependent miRNAs and their targets, reducing cancer cell aggressiveness.

Conclusions:

  • NCL is a critical regulator of specific oncogenic miRNAs in breast cancer.
  • NCL-targeting aptamers represent a promising therapeutic strategy for modulating miRNA expression in breast cancer treatment.

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