| First Author | Jiang P | Year | 2012 |
| Journal | Exp Cell Res | Volume | 318 |
| Issue | 10 | Pages | 1175-84 |
| PubMed ID | 22483937 | Mgi Jnum | J:187118 |
| Mgi Id | MGI:5435373 | Doi | 10.1016/j.yexcr.2012.03.018 |
| Citation | Jiang P, et al. (2012) MiR-34a inhibits lipopolysaccharide-induced inflammatory response through targeting Notch1 in murine macrophages. Exp Cell Res 318(10):1175-84 |
| abstractText | Inflammatory responses are complex events occurring when the host immune system fights against invading pathogens, which are double-edged swords requiring appropriate control. MicroRNAs (miRNAs), emerging as a new layer of gene-regulation mechanism, have been reported to have crucial effects on inflammation. In the current study, we identified miR-34a, previously known for its potent tumor suppressive role, to be a novel inflammation regulator. We found that the expression of miR-34a was downregulated in macrophages after lipopolysaccharide (LPS) stimulation. MiR-34a mimics decreased, while the inhibition of miR-34a increased, the expression of inflammatory cytokines tumor necrosis factor-<alpha> (TNF-<alpha>) and interleukin-6 (IL-6) in LPS treated RAW264.7 cells. Bioinformatics predictions revealed a potential binding site of miR-34a in 3' untranslated region (UTR) of Notch1 and it was further confirmed by luciferase assay. Moreover, both the mRNA and protein level of Notch1 were downregulated by miR-34a in RAW264.7. Subsequently, knockdown of Notch1 with either genetic or pharmacological inhibition exhibited similar effects as miR-34a mimics on LPS-induced macrophage inflammatory response. Furthermore, the NF-kappaB activation induced by LPS was also significantly suppressed by miR-34a. These results together identify, for the first time, miR-34a as a negative regulator in LPS-induced inflammation at least partially by targeting Notch1. Besides extending the knowledge of miR-34a from tumor suppressor to inflammation regulator, this study also provides an implication that compounds which can enhance miR-34a expression or miR-34a itself may hold a promise in anti-inflammatory drugs development. |
