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Published on: June 12, 2019
Dysregulated miR-183 inhibits migration in breast cancer cells
Aoife J Lowery1, Nicola Miller, Roisin M Dwyer
1Department of Surgery, National University of Ireland, Galway, Ireland.
Background:
The involvement of miRNAs in the regulation of fundamental cellular functions has placed them at the fore of ongoing investigations into the processes underlying carcinogenesis. MiRNA expression patterns have been shown to be dysregulated in numerous human malignancies, including breast cancer, suggesting their probable involvement as novel classes of oncogenes or tumour suppressor genes. The identification of differentially expressed miRNAs and elucidation of their functional roles may provide insight into the complex and diverse molecular mechanisms of tumorigenesis. MiR-183 is located on chromosome 7q32 and is part of a miRNA family which are dysregulated in numerous cancers. The aims of this study were to further examine the expression and functional role of miR-183 in breast cancer.
Methods:
MiR-183 expression was quantitated in primary breast tumours, tumour associated normal tissue and breast cancer cell lines using RQ-PCR. Gain of function analysis was performed in breast cancer cells using pre-miR-183 and the effect of miR-183 overexpression on cell viability, proliferation, apoptosis and migration was examined. Customized Taqman Low Density Arrays (TLDA) were used to identify dysregulated genes in breast cancer cells transfected with pre-miR-183.
Results:
We demonstrate that miR-183 is dysregulated in breast cancer and expression correlates with estrogen receptor and HER2/neu receptor expression. Induced overexpression of miR-183 inhibited migration of breast cancer cells. This finding was substantiated by RQ-PCR of mRNA from cells overexpressing miR-183 which showed dysregulation of several migration and invasion related genes. Specifically, the VIL2-coding protein Ezrin was confirmed as a target of miR-183 and downregulation of this protein was confirmed with immunocytochemistry.
Conclusions:
These findings indicate that miR-183 targets VIL2 and may play a central role in the regulation of migration and metastasis in breast cancer. Consequently, this miRNA may present an attractive target for therapeutic intervention.
Insights
MicroRNA-183 (miR-183) is dysregulated in breast cancer and inhibits cell migration by targeting the VIL2 protein, Ezrin. This finding suggests miR-183 as a potential therapeutic target for breast cancer metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of cellular functions and are frequently dysregulated in carcinogenesis.
- Aberrant miRNA expression patterns in breast cancer suggest roles as oncogenes or tumor suppressors.
- MiR-183, part of a frequently dysregulated miRNA family, is investigated for its role in breast cancer.
Purpose of the Study:
- To investigate the expression and functional role of miR-183 in breast cancer.
- To identify potential therapeutic targets for breast cancer treatment.
Main Methods:
- Quantification of miR-183 expression in breast tumors, normal tissue, and cell lines using RQ-PCR.
- Gain-of-function analysis via pre-miR-183 transfection to assess effects on cell viability, proliferation, apoptosis, and migration.
- Identification of dysregulated genes using Taqman Low Density Arrays (TLDA) in miR-183 overexpressing cells.
Main Results:
- MiR-183 expression is dysregulated in breast cancer and correlates with estrogen receptor and HER2/neu expression.
- Overexpression of miR-183 significantly inhibited breast cancer cell migration.
- RQ-PCR confirmed dysregulation of migration and invasion-related genes, with VIL2 (Ezrin) identified as a direct miR-183 target, validated by immunocytochemistry.
Conclusions:
- MiR-183 targets VIL2 (Ezrin), playing a crucial role in regulating breast cancer cell migration and metastasis.
- MiR-183 represents a promising therapeutic target for intervention in breast cancer progression.
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