DHX33 mediates p53 to regulate mevalonate pathway gene transcription in human cancers

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects Pub Date : 2023-12-22 DOI:10.1016/j.bbagen.2023.130547

Guangli Nie , Shiyun Chen , Qingzhi Song , Dongxu Zou , Maggie Li , Xiyu Tang , Yuanlian Deng , Bizhou Huang , Mengxia Yang , Guoqing Lv , Yandong Zhang

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引用次数: 0

Abstract

Tumor suppressor p53 is frequently null or mutated in human cancers. Here in this study, DHX33 protein was found to be induced in p53 null cells in vitro, and in p53 mutant lung tumorigenesis in vivo. Cholesterol metabolism through mevalonate pathway is pivotal for cell proliferation and is frequently altered in human cancers. Mice carrying mutant p53 and Kras^G12D alleles showed upregulation of mevalonate pathway gene expression. However upon DHX33 loss, their upregulation was significantly debilitated. Additionally, in many human cancer cells, DHX33 knockdown caused inhibition of mavelonate pathway gene transcription. We propose DHX33 locates downstream of mutant p53 and Ras to regulate mevalonate pathway gene transcription and thereby supports cancer development in vivo.

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DHX33 介导 p53 调节人类癌症中的甲羟戊酸通路基因转录

在人类癌症中，抑癌基因 p53 经常处于无效或突变状态。在这项研究中，我们发现 DHX33 蛋白在体外 p53 缺失的细胞和体内 p53 突变的肺部肿瘤发生中被诱导。通过甲羟戊酸途径进行的胆固醇代谢是细胞增殖的关键，在人类癌症中经常发生改变。携带突变 p53 和 KrasG12D 等位基因的小鼠显示出甲羟戊酸途径基因表达的上调。然而，一旦失去 DHX33，这些基因的上调就会明显减弱。此外，在许多人类癌细胞中，敲除 DHX33 会抑制甲羟戊酸通路基因的转录。我们认为 DHX33 位于突变 p53 和 Ras 的下游，调节甲羟戊酸通路基因的转录，从而支持体内癌症的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. General subjects 生物-生化与分子生物学

CiteScore

6.40

自引率

0.00%

发文量

139

审稿时长

30 days

期刊介绍： BBA General Subjects accepts for submission either original, hypothesis-driven studies or reviews covering subjects in biochemistry and biophysics that are considered to have general interest for a wide audience. Manuscripts with interdisciplinary approaches are especially encouraged.