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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
The effect of miR-340 over-expression on cell-cycle-related genes in triple-negative breast cancer cells
S Mohammadi Yeganeh1,2, M Vasei3, R Tavakoli4
1Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Breast cancer is a heterogeneous disease, and among all types, triple-negative breast cancer (TNBC) is characterised by high risk of recurrence. The discovery of microRNAs (miRNA) has opened the door for targeted therapy of TNBC. miR-340 down-regulation and sub-G1-accumulated cells in flowcytometry were observed in metastatic TNBC cells (data in publication), leading us to investigate the potential tumour suppressive role of this miRNA on cell-cycle-related genes. A lentiviral vector containing miR-340 was applied to over-express miR-340 in TNBC cell line, MDA-MB-231. Then, the expression of some cell-cycle-regulating genes including cyclin A2 (cyclin A2), Cyclin-dependent kinases 2 (CDK2), cyclin-dependent kinase inhibitors (P16, P18 and P27), Retinoblastoma (RB) and transcription factors (SMAD 4, SOX2 and SOX17) was investigated using quantitative RT-PCR. The results showed a decline in the expression of SOX2, P16 and P27 after miR-340 over-expression, whereas we observed an increase in the expression of cyclin A2, CDK2, SOX17, P18, SMAD 4 and RB. The over-expression of tumour suppressor genes such as RB and SOX17 and down-regulation of an oncogene such as SOX2 were in accordance to the inhibitory role of miR-340 that causes blockage of breast cancer metastasis which should be further investigated.
Insights
MicroRNA-340 (miR-340) may suppress triple-negative breast cancer (TNBC) by regulating cell-cycle genes. Overexpressing miR-340 in TNBC cells altered the expression of key genes involved in cell cycle progression and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) is aggressive with a high recurrence risk.
- MicroRNAs (miRNAs) offer potential for targeted TNBC therapies.
- miR-340 downregulation is observed in metastatic TNBC cells.
Purpose of the Study:
- To investigate the tumor-suppressive role of miR-340 in TNBC.
- To determine the effect of miR-340 on cell-cycle-related genes in TNBC.
Main Methods:
- Overexpression of miR-340 in the MDA-MB-231 TNBC cell line using a lentiviral vector.
- Quantitative RT-PCR to analyze the expression of cell-cycle regulators (cyclin A2, CDK2, P16, P18, P27, RB) and transcription factors (SMAD 4, SOX2, SOX17).
Main Results:
- miR-340 overexpression led to decreased expression of SOX2, P16, and P27.
- miR-340 overexpression resulted in increased expression of cyclin A2, CDK2, SOX17, P18, SMAD 4, and RB.
- Upregulation of tumor suppressor genes (RB, SOX17) and downregulation of oncogene SOX2 observed.
Conclusions:
- miR-340 exhibits a tumor-suppressive role in TNBC by modulating cell-cycle gene expression.
- miR-340 may inhibit breast cancer metastasis, warranting further investigation.
- This miRNA holds potential as a therapeutic target for TNBC.
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