The Role of miRNAs in Zearalenone-Promotion of TM3 Cell Proliferation

Wanglong Zheng, Wentong Fan, Nannan Feng, Nanyan Lu, Hui Zou, Jianhong Gu, Yan Yuan, Xuezhong Liu, Jianfa Bai, Jianchun Bian and Zongping Liu
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Wanglong Zheng: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China
Wentong Fan: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China
Nannan Feng: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China
Nanyan Lu: Kansas State Veterinary Diagnostic Laboratory, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA
Hui Zou: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China
Jianhong Gu: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China
Yan Yuan: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China
Xuezhong Liu: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China
Jianfa Bai: Kansas State Veterinary Diagnostic Laboratory, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA
Jianchun Bian: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China
Zongping Liu: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China

IJERPH, 2019, vol. 16, issue 9, 1-19

Abstract: Zearalenone (ZEA) is a non-steroidal estrogen mycotoxin produced by several Gibberella and Fusarium species. Accumulating evidence has indicated that ZEA strongly stimulates cell proliferation. However the detailed molecular and cellular mechanisms of ZEA-mediated induction of cell proliferation have not yet been completely explained. The aim of this study was to detect the role of miRNAs in ZEA-mediated induction of cell proliferation. The effects of ZEA on cell proliferation were assessed using a cell counting kit assay and xCELLigence system. Micro-RNA sequencing was performed after treatment of TM3 cells with ZEA (0.01 μmol/L) for different time periods (0, 2, 6 and 18 h). Cell function and pathway analysis of the miRNA target genes were performed by Ingenuity Pathway Analysis (IPA). We found that ZEA promotes TM3 cell proliferation at low concentrations. miRNA sequenceing revealed 66 differentially expressed miRNAs in ZEA-treated cells in comparison to the untreated control ( p < 0.05). The miRNA sequencing indicated that compared to control group, there were 66 miRNAs significant change ( p < 0.05) in ZEA-treated groups. IPA analysis showed that the predicated miRNAs target gene involved in cell Bio-functions including cell cycle, growth and proliferation, and in signaling pathways including MAPK and RAS-RAF-MEK-ERK pathways. Results from flow cytometry and Western Blot analysis validated the predictions that ZEA can affect cell cycle, and the MAPK signaling pathway. Taking these together, the cell proliferation induced ZEA is regulated by miRNAs. The results shed light on the molecular and cellular mechanisms for the mediation of ZEA to induce proliferation.

Keywords: zearalenone (ZEA); cell proliferation; MicroRNA; cell cycle; TM3 cell (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
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