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微囊藻毒素-LR导致HepG2细胞中肝癌相关基因转录和蛋白表达的改变。

Alterations in transcription and protein expressions of HCC-related genes in HepG2 cells caused by microcystin-LR.

作者信息

Li Xiaoyu, Zhang Xiangyang, Xie Wenjie, Zhou Chune, Li Yao, Zhang Xiuhua

机构信息

College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.

College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.

出版信息

Toxicol In Vitro. 2017 Apr;40:115-123. doi: 10.1016/j.tiv.2016.12.016. Epub 2017 Jan 3.

Abstract

Microcystin-LR (MC-LR) is the most common and toxic hepatotoxin and it could induce human hepatitis and hepatocellular carcinoma (HCC) via the route of drinking water. The aim of the present study was to determine the expressions of oncogenes c-fos, c-jun, c-myc, c-met, and N-ras and tumor suppressor gene PTEN in HepG2 cells following MC-LR-exposure to understand the possible mechanism of MC-LR-related human primary liver cancer. The results of qPCR and Western blotting showed that MC-LR-exposure at non- or sub-cytotoxic concentrations promoted the expressions of oncogenes c-fos, c-jun, c-myc, c-met, and N-ras while suppressed tumor-suppressor gene PTEN in HepG2 cells at both transcription and protein levels. This result suggests that HCC-related genes may be involved in human hepatitis and primary liver cancer caused by MC-LR. The work might be useful for evaluating the human health risk resulted from the long-term of MC-LR-exposure at low dose via drinking water route.

摘要

微囊藻毒素-LR(MC-LR)是最常见且具毒性的肝毒素,它可通过饮用水途径诱发人类肝炎和肝细胞癌(HCC)。本研究旨在确定MC-LR暴露后HepG2细胞中癌基因c-fos、c-jun、c-myc、c-met和N-ras以及肿瘤抑制基因PTEN的表达,以了解MC-LR相关人类原发性肝癌的可能机制。qPCR和蛋白质印迹结果表明,在非细胞毒性或亚细胞毒性浓度下暴露于MC-LR可促进HepG2细胞中癌基因c-fos、c-jun、c-myc、c-met和N-ras的表达,同时在转录和蛋白质水平上抑制肿瘤抑制基因PTEN。这一结果表明,HCC相关基因可能参与了由MC-LR引起的人类肝炎和原发性肝癌。该研究可能有助于评估通过饮用水途径长期低剂量暴露于MC-LR所导致的人类健康风险。

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