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Updated: Jan 20, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
MicroRNA-326 Functions as a Tumor Suppressor in Breast Cancer by Targeting ErbB/PI3K Signaling Pathway
Zahra Ghaemi1, Bahram Mohammad Soltani1, Seyed Javad Mowla1
1Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Abstract:
Breast cancer represents the most common malignancy in women worldwide and the ErbB/PI3K pathway has been found to play a crucial role in regulation of the cancer cell growth. MicroRNAs have been implicated in regulating diverse cellular pathways and therefore, understanding the link between the regulatory microRNAs and the ErbB/PI3K signaling pathway could potentially be helpful for breast cancer prevention and treatment. The aim of this study is to examine the regulatory effect of miR-326 on ErbB/PI3K signaling pathway in breast cancer development and progression. The results of qRT-PCR, RNA seq, and array data indicated that miR-326 was remarkably down-regulated in breast tumor tissues and correlated with poor survival outcome. Importantly, very low levels of miR-326 expression were found in aggressive breast cells compared to less-aggressive cell types. Mechanistically, a gene network including EGFR, ErbB2, ErbB3, AKT1, AKT2, and AKT3 targeted by miR-326, thereby providing suppression of ErbB/PI3K pathway, detected by RT-qPCR, and dual luciferase assay. In addition, Western blot analysis revealed that miR-326 upregulation decreased PI3K signaling activity by decreasing total AKT and p-AKT protein level in SKBR3 cell lines. Interestingly, up regulation of ErbB2 rescued the effect of miR-326 on miR-326 target genes. Further functional assays demonstrated that up regulation of miR-326 significantly suppressed cell growth as evidenced by cell cycle, cell cycle associated genes expression, colony formation and MTT assays and induced apoptosis, detected by Annexin V-PI. In addition, EMT markers RT-qPCR, scratch, and Transwell assays showed inhibited cellular migration and invasion following miR-326 upregulation. Altogether, our results revealed that miR-326 play a tumor-suppressive role in breast cancer through inhibiting ErbB/PI3K pathway and miR-326 may serve as a potential therapeutic target for the treatment of patients with breast cancer.
Insights
MicroRNA-326 (miR-326) is down-regulated in breast cancer, suppressing tumor growth by inhibiting the ErbB/PI3K pathway. Upregulating miR-326 shows potential for breast cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is a leading cause of death in women globally.
- The ErbB/PI3K pathway is critical for cancer cell growth and progression.
- MicroRNAs (miRNAs) are key regulators of cellular pathways, including cancer development.
Purpose of the Study:
- To investigate the role of miR-326 in regulating the ErbB/PI3K signaling pathway in breast cancer.
- To determine if miR-326 expression levels correlate with breast cancer progression and patient survival.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) and RNA sequencing to assess miR-326 expression.
- Dual luciferase assay and Western blot to confirm miR-326 targeting of ErbB/PI3K pathway components.
- Cell cycle, apoptosis, migration, and invasion assays to evaluate functional effects of miR-326.
Main Results:
- miR-326 was significantly downregulated in breast tumor tissues and associated with poor survival.
- miR-326 directly targets and suppresses the ErbB/PI3K pathway by inhibiting key genes like EGFR, AKT1, AKT2, and AKT3.
- Overexpression of miR-326 inhibited breast cancer cell proliferation, induced apoptosis, and reduced migration and invasion.
Conclusions:
- miR-326 acts as a tumor suppressor in breast cancer by inhibiting the ErbB/PI3K pathway.
- miR-326 represents a potential therapeutic target for breast cancer treatment.
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