An integrative transcriptomic analysis reveals bisphenol A exposure-induced dysregulation of microRNA expression in human endometrial cells
An integrative transcriptomic analysis reveals bisphenol A exposure-induced dysregulation of microRNA expression in human endometrial cells
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DOI：
10.1016/j.tiv.2017.02.012
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发表时间：
2017-06-01
影响因子：
3.2
通讯作者：
Chuang, Chun-Yu
中科院分区：
文献类型：
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作者：
Chou, Wei-Chun;Lee, Pei-Hsuan;Chuang, Chun-Yu
双酚A（BPA）通常用于聚碳酸酯塑料的制造。子宫内膜增生是子宫内膜癌的危险因素之一，在子宫内膜增生患者中发现较高的BPA暴露水平。在癌症的发展中已经观察到异常的microRNAs（miRNAs）调节。因此，本研究探讨BPA暴露是否会破坏miRNA调控及其基因表达与EC致癌进展的关系。在人子宫内膜癌RL 95 -2细胞中进行了miRNA和mRNA的微阵列实验，以探索与人类EC进展相对应的异常基因。根据KEGG通路和Cytoscape基因网络分析，本研究发现BPA暴露降低miR-149表达，下调DNA修复基因ARF 6（ADP-核糖基化因子6）和肿瘤蛋白p53（TP 53），上调CCNE 2（细胞周期蛋白E2），可能干扰细胞周期。BPA还增加了miR-107以抑制hedgehog信号传导因子、融合同源物抑制因子（SUFU）和GU家族锌指3（GLI 3），从而激活hedgehog信号传导，促进心肌发生相关的细胞增殖。此外，通过转染miR-149模拟物和miR-107抑制剂来减弱BPA诱导的细胞增殖。这些发现为深入了解BPA暴露对子宫内膜癌发生风险的潜在表观遗传机制提供了依据。(C)2017爱思唯尔有限公司版权所有
Bisphenol A (BPA) are commonly used in the manufacture of polycarbonate plastics. Higher BPA exposure levels have been found in patients with endometrial hyperplasia that is one of risk factors of endometrial cancer (EC). Aberrant microRNAs (miRNAs) regulation has been observed in the development of cancer. Thus, this study investigated whether BPA exposure can disrupt miRNA regulation and its gene expression regarding to EC carcinogenic progress. Microarray experiments of miRNA and mRNA were performed in human endometrial cancer RL95-2 cells with treatment of low-to-moderate (10,10(3) and 10(5) nM) BPA to explore the aberrant genes corresponding to human EC progression. According to the analysis of KEGG pathway and Cytoscape gene network, this study identified that BPA exposure reduced miR-149 expression to down-regulate DNA repair gene ARF6 (ADP-ribosylation factor 6) and tumor protein p53 (TP53), and up-regulate CCNE2 (cyclin E2) potentially to interrupt cell cycle. BPA also increased miR-107 to suppress hedgehog signaling factors, suppressor of fused homolog (SUFU) and GU family zinc finger 3 (GLI3) to activate hedgehog signaling for cell proliferation underlying cardnogenesis. Furthermore, the BPA-induced cell proliferation was attenuated by transfection with miR-149 mimic and miR-107 inhibitor. These findings provided an insight into potential epigenetic mechanism of BPA exposure on the risk of endometrial carcinogenesis.(C) 2017 Elsevier Ltd. All rights reserved.