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甲状腺。

T.

机构信息

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.

出版信息

Int J Environ Res Public Health. 2019 Apr 29;16(9):1517. doi: 10.3390/ijerph16091517.

DOI:10.3390/ijerph16091517
PMID:31035709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6540048/
Abstract

Zearalenone (ZEA) is a non-steroidal estrogen mycotoxin produced by several and 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 ( < 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.

摘要

玉米赤霉烯酮(ZEA)是由几种 和 真菌产生的非甾体雌激素真菌毒素。越来越多的证据表明,ZEA 能强烈刺激细胞增殖。然而,ZEA 介导的细胞增殖的详细分子和细胞机制尚未完全阐明。本研究旨在检测 miRNA 在 ZEA 介导的细胞增殖诱导中的作用。通过细胞计数试剂盒测定和 xCELLigence 系统评估 ZEA 对细胞增殖的影响。用 ZEA(0.01 μmol/L)处理 TM3 细胞不同时间(0、2、6 和 18 h)后,进行微 RNA 测序。通过 Ingenuity Pathway Analysis(IPA)对 miRNA 靶基因的细胞功能和途径进行分析。我们发现 ZEA 在低浓度时促进 TM3 细胞增殖。与未处理对照组相比,miRNA 序列分析显示 ZEA 处理细胞中有 66 个差异表达的 miRNA(p<0.05)。miRNA 测序表明,与对照组相比,ZEA 处理组中有 66 个 miRNA 显著变化(p<0.05)。IPA 分析显示,预测的 miRNA 靶基因参与细胞生物功能,包括细胞周期、生长和增殖,以及信号通路,包括 MAPK 和 RAS-RAF-MEK-ERK 通路。流式细胞术和 Western Blot 分析的结果验证了 ZEA 可以影响细胞周期和 MAPK 信号通路的预测。综上所述,ZEA 诱导的细胞增殖受 miRNAs 调节。这些结果揭示了 ZEA 介导增殖的分子和细胞机制。

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