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镉暴露对 HepG2 细胞的全基因组分析及 microRNAs 调控

Whole genome analysis and microRNAs regulation in HepG2 cells exposed to cadmium.

机构信息

Institute for Health and Consumer Protection, Molecular Biology and Genomics Unit, Joint Research Centre, Ispra (VA), Italy.

出版信息

ALTEX. 2012;29(2):173-82. doi: 10.14573/altex.2012.2.173.

DOI:10.14573/altex.2012.2.173
PMID:22562489
Abstract

Cadmium (Cd) is a metal known to be toxic and carcinogenic, but its mechanism of action remains to be fully elucidated. We investigated the gene expression modulation in the human hepatoma cell line HepG2 after exposure to 2 μM and 10 μM Cd using an Agilent microarray. Furthermore, we evaluated the microRNA modulation after exposure to 10 μM Cd with a Low Density Array. At the low concentration only eleven genes belonging to the metallothionein familiy were regulated. At the higher concentration the pathway enrichment analysis for the 536 up-regulated genes showed a large number of pathways related to cancer, whereas the 424 down-regulated genes were enriched on pathways correlated to liver function. A large percentage of modified microRNAs belonged to the let-7 family, which is considered to have oncosuppressor functions. Several pathways connected to cancer were regulated at the transcription level, and miRNAs had a potential impact on the modulation of this regulation.

摘要

镉(Cd)是一种已知的有毒和致癌金属,但它的作用机制仍有待充分阐明。我们使用安捷伦微阵列研究了暴露于 2 μM 和 10 μM Cd 后人肝癌细胞系 HepG2 中的基因表达调节。此外,我们还使用低密度阵列评估了暴露于 10 μM Cd 后的 microRNA 调节。在低浓度下,只有 11 种属于金属硫蛋白家族的基因受到调节。在较高浓度下,对 536 个上调基因的通路富集分析显示,与癌症相关的通路数量较多,而 424 个下调基因富集在与肝功能相关的通路中。大量修饰后的 microRNAs 属于 let-7 家族,该家族被认为具有肿瘤抑制功能。与癌症相关的几个途径在转录水平上受到调节,miRNAs 可能对这种调节的调节有潜在影响。

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