Modulation of microRNA expression by budesonide, phenethyl isothiocyanate and cigarette smoke in mouse liver and lung
Modulation of microRNA expression by budesonide, phenethyl isothiocyanate and cigarette smoke in mouse liver and lung
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DOI：
10.1093/carcin/bgq037
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发表时间：
2010-05-01
期刊：
影响因子：
4.7
通讯作者：
De Flora, Silvio
中科院分区：
文献类型：
--
作者：
Izzotti, Alberto;Larghero, Patrizia;De Flora, Silvio
尽管microrna （miRNA）在癌症研究中得到了广泛的研究，但在癌变过程的早期阶段，致癌物和/或保护因子对其的调控作用却很少受到关注。本研究旨在评估新生小鼠暴露于环境香烟烟雾（ECS）和化学预防剂治疗时mRNA表达的调节。出生后立即开始接触ECS，并在断奶后2周。此后，各组小鼠每天在饮食中服用布地奈德（BUD）或异硫氰酸苯乙酯（PEITC）。通过miRNA芯片检测576个miRNA在肝脏和肺部的表达情况。在假暴露小鼠中，mirna在肝脏中的表达往往高于肺。ECS下调了肺中一些mirna的表达，而在肝脏中观察到混合改变。PEITC和BUD对肺的生理状况没有实质性的影响，而两种药物在肝脏中引起强烈的变化，反映了炎症、DNA和蛋白质损伤、细胞应激、增殖和凋亡等损伤机制的发生。PEITC和BUD保护肺免受ecs诱导的miRNA表达改变，但在肝脏中表现出一些不利影响。
Although microRNAs (miRNA) have extensively been investigated in cancer research, less attention has been paid to their regulation by carcinogens and/or protective factors in early stages of the carcinogenesis process. The present study was designed to evaluate the modulation of mRNA expression as related to exposure of neonatal mice to environmental cigarette smoke (ECS) and to treatment with chemopreventive agents. Exposure to ECS started immediately after birth and for 2 weeks after weaning. Thereafter, groups of mice received daily either budesonide (BUD) or phenethyl isothiocyanate (PEITC) with the diet. The expression of 576 miRNAs was evaluated by miRNA microarray in liver and lung. In sham-exposed mice, the expression of miRNAs tended to be higher in liver than in lung. ECS downregulated the expression of a number of miRNAs in lung, whereas mixed alterations were observed in liver. PEITC and BUD did not substantially affect the physiological situation in lung, whereas both agents caused intense variations in liver, reflecting the occurrence of damage mechanisms, such as inflammation, DNA and protein damage, cellular stress, proliferation and apoptosis. PEITC and BUD protected the lung from ECS-induced alterations of miRNA expression but exhibited some adverse effects in liver.