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Tumour Biol. 2018 Aug;40(8):1010428318791887. doi: 10.1177/1010428318791887.

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

Author information

1
1 Department of Radiation Therapy-Radiation Oncology, University Hospital Münster, Münster, Germany.
2
2 Department of Gynecology and Obstetrics, University Hospital Münster, Münster, Germany.

Abstract

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.

KEYWORDS:

BRCA; Breast cancer; cancer stem cells; mammospheres; miR-142-3p; radiation

PMID:
30091683
DOI:
10.1177/1010428318791887
[Indexed for MEDLINE]

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