Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells

Constitutively active NF-kB is a functioning feature of many cancers.Mir-146a and miR-146b have been shown to downregulate 2 branches of the upstream cascade (IL-1 and Toll-like) through their repression of IRAK1 and TRAF6. In MDA-MB-231 cells ectopic expression of these miRNAs reduced phosphorylation of the inhibitor IkBa and NF-kB levels concomittantly by 70%. These cells showed a 80% and 60% loss of invasive capacity and migration respectively. siRNA-mediated inhibition of IkBa restored more than half of the NF-kB levels, indicating other pathways affected by these miRNAs to which end EGFR has also been identified as a target.

[cta][Oncogene][buck institute]