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染料木黄酮使 CHD5 启动子去甲基化,并抑制体内神经母细胞瘤的生长。

Genistein demethylates the promoter of CHD5 and inhibits neuroblastoma growth in vivo.

机构信息

Department of Pediatric Surgery, Children's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai 200040, PR China.

出版信息

Int J Mol Med. 2012 Nov;30(5):1081-6. doi: 10.3892/ijmm.2012.1118. Epub 2012 Sep 6.

Abstract

Neuroblastoma (NB) is a type of tumor usually found in children under 5 years of age, which originates from lesions in the nervous system and has fast growth and early transformation characteristics. Similar to other cancer types, some typical tumor suppressor genes (TSGs), such as P53 and CHD5 are silenced in NB because of high methylation at promoter zones. In the present study, our results showed that genistein, an element found in soy, is an epigenetic modifier able to decrease hypermethylation levels of CHD5, and enhances the expression of CHD5 as well as p53, possibly contributing to inhibition of NB growth in vivo and tumor microvessel formation. Furthermore, genistein acts as a DNA methyltransferase (DNMT) inhibitor to significantly decrease the expression of DNMT3b. Our study indicates that genistein plays an important role in inhibiting NB growth in vivo, probably preventing tumorigenesis risk as a kind of therapeutic agent for NB treatment in the future.

摘要

神经母细胞瘤(NB)是一种通常发生在 5 岁以下儿童的肿瘤,起源于神经系统病变,具有生长迅速和早期转化的特点。与其他癌症类型一样,一些典型的肿瘤抑制基因(TSGs),如 P53 和 CHD5,由于启动子区域的高甲基化而失活。在本研究中,我们的结果表明,大豆中的一种成分染料木黄酮是一种表观遗传修饰物,能够降低 CHD5 的过度甲基化水平,并增强 CHD5 和 p53 的表达,可能有助于抑制体内 NB 的生长和肿瘤微血管的形成。此外,染料木黄酮作为一种 DNA 甲基转移酶(DNMT)抑制剂,可显著降低 DNMT3b 的表达。我们的研究表明,染料木黄酮在体内抑制 NB 生长中发挥重要作用,可能作为一种治疗剂,预防肿瘤发生的风险,用于未来 NB 的治疗。

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