MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFα.
MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFα.
复制标题
DOI：
10.1158/0008-5472.can-12-0639
复制
发表时间：
2012-09-15
期刊：
影响因子：
11.2
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Zhang X;Ng WL;Wang P;Tian L;Werner E;Wang H;Doetsch P;Wang Y
MicroRNA-21 （miR-21）是一种在大多数人类肿瘤中过表达的肿瘤细胞，它通过作用于多个靶点来促进恶性肿瘤的生长和进展。在这里，我们通过证明miR-21调节促进肿瘤发生的活性氧（ROS）的形成，扩大了miR-21在癌症中的影响。miR-21介导这一功能的关键靶点是SOD3和TNF-a。我们发现miR-21抑制超氧化物向过氧化氢的代谢，通过内源性基础活性或暴露于电离辐射，通过指导减弱SOD3或通过限制TNF-a产生的间接机制，从而降低SOD2水平。重要的是，这两种效应都有助于提高红外诱导的细胞转化。因此，我们的研究结果表明，miR-21在很大程度上是通过调控细胞ROS水平促进肿瘤发生的。
MicroRNA-21 (miR-21) is an oncomir overexpressed in most human tumors where it promotes malignant growth and progression by acting on multiple targets. Here we broaden the impact of miR-21 in cancer by demonstrating that it regulates formation of reactive oxygen species (ROS) that promote tumorigenesis. Key targets of miR-21 in mediating this function were SOD3 and TNF-a. We found that miR-21 inhibited the metabolism of superoxide to hydrogen peroxide, produced either by endogenous basal activities or exposure to ionizing radiation, by directing attenuating SOD3 or by an indirect mechanism that limited TNF-a production, thereby reducing SOD2 levels. Importantly, both effects contributed to an elevation of IR-induced cell transformation. Our findings therefore establish that miR-21 promotes tumorigenesis to a large extent through its regulation of cellular ROS levels.