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Updated: Apr 12, 2026
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Targeting of miR9/NOTCH1 interaction reduces metastatic behavior in triple-negative breast cancer
Samira Mohammadi-Yeganeh1,2, Ardalan Mansouri2, Mahdi Paryan3,4
1Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, 6th Floor, 2th SBUMS Bldg., Next to Ayatollah Taleghani Hospital, Velenjak, Tehran, 198396-3113, Iran.
Abstract:
Many reports have indicated deregulation of a variety of microRNAs (miRNAs) in human cancers. In this study, we appraised miR-9 correlation with NOTCH1 involved in Notch signaling in metastatic breast cancer. The Notch signaling pathway has been approved to be associated with the development and progression of many human cancers, including breast cancer, but the precise mechanism has remained unknown. To the best of our knowledge, this is the first study that introduces miR-9 and NOTCH1 correlation as an effective factor in breast cancer. We found that miR-9 expression was decreased in MDA-MB-231 breast cancer cells compared with MCF-10A normal breast cell line. However, NOTCH1 was upregulated in the metastatic breast cancer cells. Furthermore, luciferase assay revealed a significant inverse correlation between miR-9 and NOTCH1. Overexpression of Notch signaling via Notch1 intracellular domain in MDA-MB-231 cell line was suppressed by lentiviruses expressing miR-9. Taken together, the results obtained by MTT, flow cytometry, migration, and wound healing assays showed that it is possible to inhibit metastasis and induce pro-apoptotic state by induction of miR-9 expression in MDA-MB-231 cells but with no effect on cell proliferation. These results shows that miR-9, by direct targeting of NOTCH1, can reveal a suppressor-like activity in metastatic breast cancer cells.
Insights
This study reveals that reduced microRNA-9 (miR-9) expression correlates with increased NOTCH1 in metastatic breast cancer. Restoring miR-9 suppresses cancer cell metastasis and promotes apoptosis by targeting NOTCH1.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are frequently deregulated in human cancers.
- The Notch signaling pathway, involving NOTCH1, is implicated in cancer development but its precise role in breast cancer remains unclear.
Purpose of the Study:
- To investigate the correlation between miR-9 and NOTCH1 in metastatic breast cancer.
- To explore the potential of miR-9 as a therapeutic target for inhibiting breast cancer metastasis.
Main Methods:
- Comparison of miR-9 and NOTCH1 expression in metastatic breast cancer cells (MDA-MB-231) versus normal breast cells (MCF-10A).
- Luciferase assay to confirm the direct interaction between miR-9 and NOTCH1.
- Overexpression of miR-9 using lentiviral vectors in cancer cells.
- Assessment of cell proliferation, apoptosis, migration, and wound healing.
Main Results:
- miR-9 expression was significantly decreased, while NOTCH1 was upregulated in metastatic breast cancer cells.
- A direct inverse correlation between miR-9 and NOTCH1 was confirmed.
- miR-9 induction suppressed Notch signaling and inhibited MDA-MB-231 cell migration and metastasis.
- miR-9 overexpression induced apoptosis without affecting cell proliferation.
Conclusions:
- miR-9 acts as a tumor suppressor in metastatic breast cancer by directly targeting and downregulating NOTCH1.
- Restoring miR-9 expression offers a potential therapeutic strategy to inhibit metastasis and induce apoptosis in breast cancer.
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