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Mol Carcinog. 2018 Apr;57(4):483-493. doi: 10.1002/mc.22772. Epub 2017 Dec 29.

NF-κB-regulated miR-155, via repression of QKI, contributes to the acquisition of CSC-like phenotype during the neoplastic transformation of hepatic cells induced by arsenite.

Chen C1,2, Luo F1,2, Yang Q1,2, Wang D3, Yang P4, Xue J1,2, Dai X1,2, Liu X1,2, Xu H1,2, Lu J4, Zhang A3, Liu Q1,2.

Author information

1
Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
2
The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
3
The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
4
The School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic China.

Abstract

Chronic exposure to arsenite can cause various human tumors. For the initiation and recurrence of human liver cancer, the acquisition of CSC-like properties is essential. In various cancers, microRNAs (miRNAs) act as regulators in induction of CSC-like properties. Liver cancers over-express miR-155, but the mechanism relating miR-155 and arsenite-induced liver cancer is unknown. Here, we show that long-term exposure of L-02 cells to arsenite increases miR-155 levels by activation of NF-κB and leads to the acquisition of CSC-like properties. In spheroids formed from arsenite-transformed L-02 cells, the levels of miR-155 positively relate to the levels of CD90, EpCAM, and OCT4. Inhibition of miR-155, by reduction of SOX2 and OCT4, results in suppression of spheroid formation. Luciferase reporter assays indicate that QKI is a target of miR-155. Inhibition of QKI expression by miR-155 promotes arsenite-induced acquisition of CSC-like properties, whereas QKI over-expression has the opposite effect. Collectively, the findings demonstrate that miR-155, driven by NF-κB, reduces QKI expression and is involved in acquisition of the CSC-like phenotype during neoplastic transformation of hepatic cells induced by arsenite.

KEYWORDS:

NF-κB; QKI; arsenite; cancer stem cells (CSCs); miR-155

PMID:
29240254
DOI:
10.1002/mc.22772
[Indexed for MEDLINE]

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