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CYP1A1 是 miR-892a 介导的转录后抑制的靶标。

CYP1A1 is a target of miR-892a-mediated post-transcriptional repression.

机构信息

Functional Genoproteome Research Centre and LIFEnGENE Inc, Seoul 143-701, Republic of Korea.

出版信息

Int J Oncol. 2012 Jul;41(1):331-6. doi: 10.3892/ijo.2012.1418. Epub 2012 Mar 28.

Abstract

Cytochrome P450 1A1 (CYP1A1) is a member of the cytochrome p450 enzyme family, which is involved in the metabolisms of carcinogenic metabolites, such as benzo(a)pyrene. In this study, we identified miR-892a as a negative regulator of CYP1A1 expression. Luciferase assays revealed a sequence in the 3'-untranslated region of CYP1A1 that displayed a perfect match with miR-892a, and revealed that this sequence was a specific miR-892a target site. The overexpression of miR‑892a inhibited the expression of the CYP1A1 protein, and the miR‑892a antagonist increased CYP1A1 expression. Of note, benzo(a)pyrene, a major inducer of CYP1A1 transcription, decreased the expression of miR-892a. Moreover, the miR-892a-induced CYP1A1 repression inhibited the benzo(a)pyrene-mediated decrease in cell viability. These data provide insight into the CYP1A1 regulatory network.

摘要

细胞色素 P450 1A1(CYP1A1)是细胞色素 p450 酶家族的成员,参与致癌代谢物如苯并(a)芘的代谢。在这项研究中,我们鉴定出 miR-892a 是 CYP1A1 表达的负调控因子。荧光素酶检测显示 CYP1A1 的 3'-非翻译区存在一个与 miR-892a 完全匹配的序列,表明该序列是 miR-892a 的一个特定靶位点。miR-892a 的过表达抑制了 CYP1A1 蛋白的表达,而 miR-892a 的拮抗剂则增加了 CYP1A1 的表达。值得注意的是,苯并(a)芘是 CYP1A1 转录的主要诱导剂,它降低了 miR-892a 的表达。此外,miR-892a 诱导的 CYP1A1 抑制作用抑制了苯并(a)芘介导的细胞活力下降。这些数据为 CYP1A1 的调控网络提供了新的见解。

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