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.

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.

• Authors: Chao Chen, Fei Luo, Qianlei Yang, Dapeng Wang, Ping Yang, Junchao Xue, Xiangyu Dai, Xinlu Liu, Hui Xu, Jiachun Lu, Aihua Zhang, Qizhan Liu
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 57 Issue 4 Pg. 483-493 (04 2018) ISSN: 1098-2744 [Electronic] United States
• PMID: 29240254 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Arsenites
• MIRN155 microRNA, human
• MicroRNAs
• NF-kappa B
• Octamer Transcription Factor-3
• POU5F1 protein, human
• QKI protein, human
• RNA-Binding Proteins
• SOX2 protein, human
• SOXB1 Transcription Factors

Topics

• Arsenites (pharmacology)
• Base Sequence
• Cell Line
• Cell Transformation, Neoplastic (drug effects, genetics, metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Hepatocytes (drug effects, metabolism)
• Humans
• MicroRNAs (genetics)
• NF-kappa B (metabolism)
• Neoplastic Stem Cells (metabolism)
• Octamer Transcription Factor-3 (genetics, metabolism)
• Phenotype
• RNA-Binding Proteins (genetics, metabolism)
• SOXB1 Transcription Factors (genetics, metabolism)
• Sequence Homology, Nucleic Acid
• Spheroids, Cellular (drug effects, metabolism)