title: miR-141 as potential suppressor of β-catenin in breast cancer.
abstract: Triple negative breast cancer (TNBC) is well known for its heterogeneous features and lack of targeted therapy. A variety of cell signaling pathways have been linked to the initiation and progression of these tumors where canonical Wnt signaling is one of the main candidate pathways. Considering past literatures on this matter and negative reports regarding mutations in β-catenin gene (CTNNB1), we focus our attention to another level of gene expression control level, microRNAs (miRNAs). For proper miRNA target detection, we utilized bioinformatics as a relatively new and reliable tool for miRNA: mRNA prediction. MDA-MB-231 (invasive breast cancer) and MCF-10A (normal breast) cell lines were chosen as models. We used different bioinformatic tools such as TargetScan, miRanda, etc. For miRNA targeting CTNNB1-3´UTR confirmation, luciferase assay was carried out. miRNA expression was induced in cell lines through viral constructs expressing desired miRNA. Quantitative real-time PCR was performed for the measurement of expression levels of selected miRNA and target gene. miR-141 was selected via expanded search among various bioinformatic tools. miR-141 expression level was downregulated in MDA-MB-231 cell line, and CTNNB1 gene expression was upregulated. After transduction with viral construct, miR-141 expression was elevated in both cell lines, and gene expression was notably decreased. β-Catenin can be considered as one of the main players in these tumors' pathogenesis. Also, it is the potential target of miR-141, in which its downregulation was detected in cell lines, and can be considered as a promising new targeted approach toward TNBC.
authors.affiliation: Department of New Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Nairi
authors.initials: N
authors.lastname: Abedi
authors.affiliation: Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. s.mohammadiyeganeh@sbmu.ac.ir.|Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. s.mohammadiyeganeh@sbmu.ac.ir.
authors.forename: Samira
authors.initials: S
authors.lastname: Mohammadi-Yeganeh
authors.affiliation: Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ameneh
authors.initials: A
authors.lastname: Koochaki
authors.affiliation: Department of New Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Karami
authors.affiliation: Department of Research and Development, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran. mparyan@pasteur.ac.ir.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Paryan
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin
keywords: CTNNB1 gene; Luciferase assay; Triple negative breast cancer; Wnt signaling; miRNA