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Updated: Jun 25, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
microRNA-205 regulates HER3 in human breast cancer
Marilena V Iorio1, Patrizia Casalini, Claudia Piovan
1Molecular Biology Unit, Department of Experimental Oncology, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milano, Italy.
Abstract:
An increasing amount of experimental evidence shows that microRNAs can have a causal role in breast cancer tumorigenesis as a novel class of oncogenes or tumor suppressor genes, depending on the targets they regulate. HER2 overexpression is a hallmark of a particularly aggressive subset of breast tumors, and its activation is strictly dependent on the trans-interaction with other members of HER family; in particular, the activation of the PI3K/Akt survival pathway, so critically important in tumorigenesis, is predominantly driven through phosphorylation of the kinase-inactive member HER3. Here, we show that miR-205, down-modulated in breast tumors compared with normal breast tissue, directly targets HER3 receptor, and inhibits the activation of the downstream mediator Akt. The reintroduction of miR-205 in SKBr3 cells inhibits their clonogenic potential and increases the responsiveness to tyrosine-kinase inhibitors Gefitinib and Lapatinib, abrogating the HER3-mediated resistance and restoring a potent proapoptotic activity. Our data describe miR-205 as a new oncosuppressor gene in breast cancer, able to interfere with the proliferative pathway mediated by HER receptor family. Our study also provides experimental evidence suggesting that miR-205 can improve the responsiveness to specific anticancer therapies.
Insights
MicroRNA-205 (miR-205) acts as a tumor suppressor in breast cancer by targeting the HER3 receptor and inhibiting the Akt pathway. Restoring miR-205 enhances sensitivity to cancer therapies.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs play critical roles in breast cancer, acting as oncogenes or tumor suppressors.
- HER2-overexpressing breast tumors are aggressive and rely on HER family interactions, particularly HER3, for PI3K/Akt pathway activation.
Purpose of the Study:
- To investigate the role of miR-205 in breast cancer.
- To determine if miR-205 targets the HER3 receptor and affects downstream signaling.
- To assess the therapeutic potential of miR-205 in breast cancer treatment.
Main Methods:
- Quantitative analysis of miR-205 expression in breast tumors versus normal tissue.
- Direct targeting of HER3 receptor by miR-205 was confirmed.
- Assessment of Akt pathway activation and cell proliferation (clonogenic potential) in response to miR-205 modulation.
- Evaluation of drug sensitivity to Gefitinib and Lapatinib upon miR-205 reintroduction.
Main Results:
- miR-205 is downregulated in breast tumors compared to normal tissue.
- miR-205 directly targets and downregulates the HER3 receptor, inhibiting Akt activation.
- Reintroduction of miR-205 into SKBr3 cells reduced clonogenic potential and restored sensitivity to tyrosine-kinase inhibitors.
- miR-205 abrogated HER3-mediated resistance and promoted apoptosis.
Conclusions:
- miR-205 functions as a tumor suppressor gene in breast cancer.
- miR-205 interferes with the HER receptor family-mediated proliferative pathway.
- miR-205 holds potential for improving patient response to specific anticancer therapies.
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