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MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFα.

ABSTRACT: MicroRNA-21 (miR-21) is an oncomir overexpressed in most human tumors in that it promotes malignant growth and progression by acting on multiple targets. Here, we broaden the impact of miR-21 in cancer by showing that it regulates the formation of reactive oxygen species (ROS) that promote tumorigenesis. Key targets of miR-21 in mediating this function were SOD3 and TNFα. We found that miR-21 inhibited the metabolism of superoxide to hydrogen peroxide, produced either by endogenous basal activities or exposure to ionizing radiation (IR), by directing attenuating SOD3 or by an indirect mechanism that limited TNFa 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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC3445705 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFα.

Zhang Xiangming X Ng Wooi-Loon WL Wang Ping P Tian Linlin L Werner Erica E Wang Huichen H Doetsch Paul P Wang Ya Y

Cancer research 20120725 18

MicroRNA-21 (miR-21) is an oncomir overexpressed in most human tumors in that it promotes malignant growth and progression by acting on multiple targets. Here, we broaden the impact of miR-21 in cancer by showing that it regulates the formation of reactive oxygen species (ROS) that promote tumorigenesis. Key targets of miR-21 in mediating this function were SOD3 and TNFα. We found that miR-21 inhibited the metabolism of superoxide to hydrogen peroxide, produced either by endogenous basal activit ...[more]

PMID: 22836756

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