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首页> 外文期刊>Cell cycle >A knockdown with smoke model reveals FHIT as a repressor of Heme oxygenase 1
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A knockdown with smoke model reveals FHIT as a repressor of Heme oxygenase 1

机译：带有烟雾模型的组合显示FHIT是血红素加氧酶1的阻遏物

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Fragile histidine triad (FHIT) gene deletions are among the earliest and most frequent events in carcinogenesis, particularly in carcinogen-exposed tissues. Though FHIT has been established as an authentic tumor suppressor, the mechanism underlying tumor suppression remains opaque. Most experiments designed to clarify FHIT function have analyzed the consequence of re-expressing FHIT in FHIT-negative cells. However, carcinogenesis occurs in cells that transition from FHIT-positive to FHIT-negative. To better understand cancer development, we induced FHIT loss in human bronchial epithelial cells with RNA interference. Because FHIT is a demonstrated target of carcinogens in cigarette smoke, we combined FHIT silencing with cigarette smoke extract (CSE) exposure and measured gene expression consequences by RNA microarray. The data indicate that FHIT loss enhances the expression of a set of oxidative stress response genes after exposure to CSE, including the cytoprotective enzyme heme oxygenase 1 (HMOX1) at the RNA and protein levels. Data are consistent with a mechanism in which Fhit protein is required for accumulation of the transcriptional repressor of HMOX1, Bach1 protein. We posit that by allowing superinduction of oxidative stress response genes, loss of FHIT creates a survival advantage that promotes carcinogenesis.
机译：易碎的组氨酸三联体（FHIT）基因缺失是致癌作用最早，最频繁的事件之一，特别是在致癌物质暴露的组织中。尽管FHIT已被确立为真正的肿瘤抑制因子，但抑制肿瘤的机制仍不明确。大多数旨在阐明FHIT功能的实验都分析了在FHIT阴性细胞中重新表达FHIT的结果。但是，癌变发生在从FHIT阳性转变为FHIT阴性的细胞中。为了更好地了解癌症的发展，我们在RNA干扰下诱导了人支气管上皮细胞的FHIT丢失。由于FHIT已被证明是香烟烟雾中致癌物的靶标，因此我们将FHIT沉默与香烟烟雾提取物（CSE）暴露相结合，并通过RNA微阵列测量了基因表达的后果。数据表明，FHIT缺失会增强一组氧化应激反应基因在CSE中的表达，包括在RNA和蛋白质水平上的细胞保护酶血红素加氧酶1（HMOX1）。数据与其中Fhit蛋白是HMOX1，Bach1蛋白的转录阻遏物积累所需的机制是一致的。我们认为，通过允许氧化应激反应基因的超诱导，FHIT的丧失产生了促进癌变的生存优势。

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