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Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
Published on: June 7, 2016
MicroRNAs in breast cancer pathogenesis
1Research Laboratory, Department of Gynecology and Obstetrics, Münster University Hospital, Münster, Germany. mgotte@uni-muenster.de
Abstract:
Micro RNAs (miRNAs) are small non-coding RNAs which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, expression of miRNAs is frequently dysregulated. Both tumor suppressor activity and oncogenic properties have been assigned to specific miRNAs, which modulate virtually all relevant stages of breast cancer progression, including tumor cell proliferation, apoptosis resistance, cancer cell migration, invasiveness and metastasis, tumor angiogenesis and cancer stem cell self-renewal. miRNA expression has been studied by microarray profiling, bead-based technologies and quantitative real-time PCR in archived formalin-fixed paraffin-embedded tumor specimens as well as blood and serum samples, allowing to identify specific miRNAs as novel diagnostic, prognostic and predictive markers. Moreover, the investigation of single nucleotide polymorphisms both in putative miRNA binding sites in the 3'UTRs of target genes, as well as in miRNA-endocing genes have revealed their diagnostic potential. In vitro experiments employing established breast cancer cell lines and in vivo xenograft studies have demonstrated the efficacy of oligonucleotide-based overexpression and inhibitor approaches of miRNA-targeted experimental therapies. Numerous studies have identified specific targets of miRNA action in breast cancer, including the established markers Her2/neu and ERalpha, TP53, and markers of angiogenesis. The future application of locked-nucleic acid miRNA inhibitors, and synergistic approaches involving conventional breast cancer therapeutics opens up promising new perspectives in breast cancer therapy.
Insights
MicroRNAs (miRNAs) are key regulators in breast cancer, impacting progression and offering new diagnostic and therapeutic targets. Dysregulated miRNA expression presents opportunities for novel breast cancer treatments.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression.
- miRNA dysregulation is common in breast cancer, influencing tumor progression.
- miRNAs exhibit both tumor-suppressive and oncogenic roles in breast cancer.
Purpose of the Study:
- To review the role of miRNAs in breast cancer progression.
- To explore miRNAs as diagnostic, prognostic, and predictive markers.
- To discuss miRNA-targeted therapies for breast cancer.
Main Methods:
- Analysis of miRNA expression profiling data (microarrays, qPCR).
- Investigation of miRNA single nucleotide polymorphisms (SNPs).
- In vitro cell line and in vivo xenograft studies of miRNA-targeting therapies.
Main Results:
- miRNAs modulate key breast cancer hallmarks like proliferation, apoptosis, migration, and angiogenesis.
- Specific miRNAs identified as potential diagnostic and prognostic markers.
- Oligonucleotide-based miRNA therapies show efficacy in preclinical models.
Conclusions:
- miRNAs are crucial in breast cancer development and progression.
- miRNA-based diagnostics and therapeutics hold significant promise.
- Targeted miRNA therapies, including locked-nucleic acid inhibitors, offer new treatment avenues.
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