miR-142-3p attenuates breast cancer stem cell characteristics and decreases radioresistance in vitro

Effectively targeting cancer stem cells, a subpopulation of tumorigenic, aggressive, and radioresistant cells, holds therapeutic promise. However, the effects of the microRNA miR-142-3p, a small endogenous regulator of gene expression on breast cancer stem cells, have not been investigated. This stu...

Authors: Troschel, Fabian Martin
Böhly, Nicolas
Borrmann, Katrin
Braun, Timo
Schwickert, Alexander
Kiesel, Ludwig
Eich, Hans-Theodor
Götte, Martin
Greve, Burkhard
Division/Institute:FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2018
Date of publication on miami:16.05.2019
Modification date:16.05.2019
Edition statement:[Electronic ed.]
Source:Tumor Biology 40 (2018) 8, 1-10
Subjects:Breast cancer; cancer stem cells; miR-142-3p; radiation; BRCA; mammospheres
DDC Subject:610: Medizin und Gesundheit
License:CC BY-NC 4.0
Language:English
Funding:Finanziert durch den Open-Access-Publikationsfonds 2018 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
URN:urn:nbn:de:hbz:6-84199463979
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-84199463979
Other Identifiers:DOI: 10.1177/1010428318791887
Digital documents:artikel_greve_2018.pdf

Effectively targeting cancer stem cells, a subpopulation of tumorigenic, aggressive, and radioresistant cells, holds therapeutic promise. However, the effects of the microRNA miR-142-3p, a small endogenous regulator of gene expression on breast cancer stem cells, have not been investigated. This study identifies the influence of miR-142-3p on mammary stemness properties and breast cancer radioresistance to establish its role in this setting. miR-142-3p precursor transfection was performed in MDA-MB-468, HCC1806, and MCF-7 cells, and stem cell markers CD44, CD133, ALDH1 activity and mammosphere formation were measured. β-catenin, the canonical wnt signaling effector protein, was quantified by Western blots and cell fluorescence assays both in miR-142-3p–overexpressing and anti–miR-142-3p–treated cells. Radiation response was investigated by colony formation assays. Levels of BRCA1, BRCA2, and Bod1 in miR-142-3p–overexpressing cells as well as expression of miR-142-3p, Bod1, KLF4, and Oct4 in sorted CD44+/CD24–/low cells were determined by quantitative polymerase chain reaction. miR-142-3p overexpression resulted in a strong decline in breast cancer stem cell characteristics with a decrease in CD44, CD133, ALDH1, Bod1, BRCA2, and mammosphere formation as well as reduced survival after irradiation. miR-142-3p expression was strongly reduced in sorted CD44+/CD24–/low stem cells, while Bod1, Oct4, and KLF4 were overexpressed. β-catenin levels strongly decreased after miR-142-3p overexpression, but not after anti–miR-142-3p treatment. We conclude that miR-142-3p downregulates cancer stem cell characteristics and radioresistance in breast cancer, mediated by a reduced role of β-catenin in miR-142-3p–overexpressing cells. miR-142-3p might therefore help to target cancer stem cells.