TY  - JOUR
AB  - 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.
AU  - Troschel, Fabian Martin
AU  - Böhly, Nicolas
AU  - Borrmann, Katrin
AU  - Braun, Timo
AU  - Schwickert, Alexander
AU  - Kiesel, Ludwig
AU  - Eich, Hans-Theodor
AU  - Eich, Hans Theodor
AU  - Eich, Hans Theodor
AU  - Eich, Hans Theodor
AU  - Götte, Martin
AU  - Greve, Burkhard
DA  - 2018-08-09
DO  - 10.1177/1010428318791887
KW  - Breast cancer
KW  - cancer stem cells
KW  - miR-142-3p
KW  - radiation
KW  - BRCA
KW  - mammospheres
LA  - eng
N1  - Tumor Biology 40 (2018) 8, 1-10
N1  - Finanziert durch den Open-Access-Publikationsfonds 2018 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2018-08-09
TI  - miR-142-3p attenuates breast cancer stem cell characteristics and decreases radioresistance in vitro
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-84199463979
Y2  - 2024-10-30T21:51:59
ER  -