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Updated: May 12, 2026

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
Published on: June 7, 2016
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
Abstract:
Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer.
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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