Inflammation regulates microRNA expression in cooperation with p53 and nitric oxide.
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ABSTRACT: microRNA (miRNA) are small non-coding RNA targeting mRNAs leading to their instability and diminished translation. Altered expression of miRNA is associated with cancer. Inflammation and nitric oxide modulates the development of lymphomas in p53 knockout mice and there exists a negative feedback loop between p53 and NOS2. Using a genetic strategy, we tested the hypothesis that inflammation-induced oxidative and nitrosative stress modulates miRNA expression in mouse model deficient in either p53 or NOS2. Mice treated with Corynebacterium parvum (C. parvum), to induce inflammation, clearly separated from controls by their miRNA profiles in wild-type, p53- and NOS2-knockout genetic backgrounds. C. parvum-induced inflammation significantly (p < 0.005) increased miR-21, miR-29b and miR-34a/b/c and decreased (p < 0.005) mir-29c and mir-181a/c expression in the spleen of C57BL mice. However, p53-knockout C57BL mice did not show a significant increase in the mir-34b/c or a decrease in mir-29c expression following C. parvum-induced inflammation. Expression of mir-21, mir-29b and mir-181a was independent of p53-status. NOS2-knockout C57BL mice showed a significant increase in miR-21 and miR-34a/b/c and decrease in miR-181a similar to the wild-type (WT) mice following C. parvum-induced inflammation. However, in contrast to the WT mice, miR-29b/c expression was not affected following C. parvum-induced inflammation in NOS2 knockout mice. N-acetyl cysteine, an anti-oxidant, reduced the expression of miR-21 and miR-29b in C. parvum-treated WT mice (p < 0.005) as compared with control C. parvum-treated mice. These data are consistent with the hypothesis that inflammation modulates miRNA expression in vivo and the alteration in specific miRNA under an inflammatory microenvironment, can be influenced by p53 (miR-34b/c) and NO(•) (29b/c).
SUBMITTER: Mathe E
PROVIDER: S-EPMC3299894 | biostudies-literature | 2012 Aug
REPOSITORIES: biostudies-literature
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