Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-09

AUTHORS

D Bhaumik, G K Scott, S Schokrpur, C K Patil, J Campisi, C C Benz

ABSTRACT

Cancer cells often acquire a constitutively active nuclear factor-kappaB (NF-kappaB) program to promote survival, proliferation and metastatic potential by mechanisms that remain largely unknown. Extending observations from an immunologic setting, we demonstrate that microRNA-146a and microRNA-146b (miR-146a/b) when expressed in the highly metastatic human breast cancer cell line MDA-MB-231 function to negatively regulate NF-kappaB activity. Lentiviral-mediated expression of miR-146a/b significantly downregulated interleukin (IL)-1 receptor-associated kinase and TNF receptor-associated factor 6, two key adaptor/scaffold proteins in the IL-1 and Toll-like receptor signaling pathway, known to positively regulate NF-kappaB activity. Impaired NF-kappaB activity was evident from reduced phosphorylation of the NF-kappaB inhibitor IkappaBalpha, reduced NF-kappaB DNA-binding activity and suppressed expression of the NF-kappaB target genes IL-8, IL-6 and matrix metalloproteinase-9. Functionally, miR-146a/b-expressing MDA-MB-231 cells showed markedly impaired invasion and migration capacity relative to control cells. These findings implicate miR-146a/b as a negative regulator of constitutive NF-kappaB activity in a breast cancer setting and suggest that modulating miR-146a/b levels has therapeutic potential to suppress breast cancer metastases. More... »

PAGES

onc2008171

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2008.171

DOI

http://dx.doi.org/10.1038/onc.2008.171

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046998641

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18504431


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