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血清 miR-206 和 miR-133b 的改变与 4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁酮诱导的肺癌发生有关。

Alteration of serum miR-206 and miR-133b is associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

机构信息

Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, People's Republic of China.

出版信息

Toxicol Appl Pharmacol. 2013 Mar 15;267(3):238-46. doi: 10.1016/j.taap.2013.01.002. Epub 2013 Jan 18.

Abstract

The alteration of microRNA (miRNA) expression plays an important role in chemical carcinogenesis. Presently, few reports have been published that concern the significance of circulating miRNAs in lung carcinogenesis induced by environmental carcinogens. The purpose of this study was to identify serum miRNAs that could be associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Male F344 rats were systemically administered with NNK. The rat serum differential expression profiles of miRNAs were analyzed by small RNA solexa sequencing. Using quantitative real-time PCR, the differentially expressed serum miRNAs were identified in each individual rat. Serum miR-206 and miR-133b were selected for further identification in rat serum at different stages of lung carcinogenesis; we detected the levels of serum miR-206 and miR-133b in lung cancer tissues induced by NNK. NNK causes significant alteration of serum miRNA expression. Compared to the control group, serum miR-206 and miR-133b were significantly up-regulated in the early stage of NNK-induced lung carcinogenesis. miR-206 and miR-133b exhibited low-expression in lung cancer tissues. Our results demonstrate that lung carcinogen NNK exposure changes the expression of serum miRNAs. Serum miR-206 and miR-133b could be associated with lung carcinogenesis induced by NNK.

摘要

miRNA 表达的改变在化学致癌作用中起着重要作用。目前,关于环境致癌物诱导的肺癌发生中循环 miRNA 的意义的报道很少。本研究的目的是鉴定与 4-(甲基亚硝氨基)-1-(3-吡啶基)-1-丁酮(NNK)诱导的肺癌发生相关的血清 miRNAs。雄性 F344 大鼠经系统给予 NNK。通过小 RNA solexa 测序分析 miRNA 在大鼠血清中的差异表达谱。使用定量实时 PCR 鉴定每个大鼠中差异表达的血清 miRNA。选择血清 miR-206 和 miR-133b 用于进一步鉴定 NNK 诱导的肺癌发生不同阶段的大鼠血清中的 miR-206 和 miR-133b;我们检测了 NNK 诱导的肺癌组织中血清 miR-206 和 miR-133b 的水平。NNK 导致血清 miRNA 表达发生显著改变。与对照组相比,NNK 诱导的肺癌发生早期,血清 miR-206 和 miR-133b 显著上调。miR-206 和 miR-133b 在肺癌组织中表达较低。我们的结果表明,肺致癌物 NNK 暴露改变了血清 miRNAs 的表达。血清 miR-206 和 miR-133b 可能与 NNK 诱导的肺癌发生有关。

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