title: Targeting of miR9/NOTCH1 interaction reduces metastatic behavior in triple-negative breast cancer.
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.
authors.affiliation: Department 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.|Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, 6th Floor, 2th SBUMS Bldg., Next to Ayatollah Taleghani Hospital, Velenjak, Tehran, 198396-3113, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Mohammadi-Yeganeh
authors.affiliation: Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, 6th Floor, 2th SBUMS Bldg., Next to Ayatollah Taleghani Hospital, Velenjak, Tehran, 198396-3113, Iran.
authors.forename: Ardalan
authors.initials: A
authors.lastname: Mansouri
authors.affiliation: Department of Research and Development, Production and Research Complex, Pasteur Institute of Iran, km 25, Tehran-Karaj higjway, Tehran, 315991-5111, Iran.|Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, No.9, East 2nd,, St., Farhang Blvd., Saadat Abad St., Tehran, 199777-5555, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Paryan
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051881:Receptor, Notch1 / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1
keywords: MDA-MB-231; NOTCH1; Notch signaling; breast cancer; miR-9