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Open AccessArticle

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

by Wanglong Zheng 1,2,3,4,†, Wentong Fan 1,2,3,†, Nannan Feng 1,2, Nanyan Lu 4, Hui Zou 1,2, Jianhong Gu 1,2, Yan Yuan 1,2, Xuezhong Liu 1,2, Jianfa Bai 4, Jianchun Bian 1,2,3,* and Zongping Liu 1,2,3,*
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China
Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, Jiangsu, China
Kansas State Veterinary Diagnostic Laboratory, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA
Authors to whom correspondence should be addressed.
These two authors contributed equally to this work.
Int. J. Environ. Res. Public Health 2019, 16(9), 1517;
Received: 20 February 2019 / Revised: 23 April 2019 / Accepted: 25 April 2019 / Published: 29 April 2019
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. View Full-Text
Keywords: zearalenone (ZEA); cell proliferation; MicroRNA; cell cycle; TM3 cell zearalenone (ZEA); cell proliferation; MicroRNA; cell cycle; TM3 cell
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MDPI and ACS Style

Zheng, W.; Fan, W.; Feng, N.; Lu, N.; Zou, H.; Gu, J.; Yuan, Y.; Liu, X.; Bai, J.; Bian, J.; Liu, Z. The Role of miRNAs in Zearalenone-Promotion of TM3 Cell Proliferation. Int. J. Environ. Res. Public Health 2019, 16, 1517.

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