dc.contributor.author | Xiang, Michael | |
dc.contributor.author | Birkbak, Nicolai Juul | |
dc.contributor.author | Vafaizadeh, V. | |
dc.contributor.author | Walker, Sarah Rebecca | |
dc.contributor.author | Yeh, Jennifer E | |
dc.contributor.author | Liu, Suhu | |
dc.contributor.author | Kroll, Yasmin | |
dc.contributor.author | Boldin, M. | |
dc.contributor.author | Taganov, K. | |
dc.contributor.author | Groner, B. | |
dc.contributor.author | Richardson, Andrea Lynn | |
dc.contributor.author | Frank, David Alan | |
dc.date.accessioned | 2017-04-27T19:25:53Z | |
dc.date.issued | 2014 | |
dc.identifier | Quick submit: 2014-08-08T10:09:39-04:00 | |
dc.identifier.citation | Xiang, M., N. J. Birkbak, V. Vafaizadeh, S. R. Walker, J. E. Yeh, S. Liu, Y. Kroll, et al. 2014. “STAT3 Induction of miR-146b Forms a Feedback Loop to Inhibit the NF- B to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes.” Science Signaling 7 (310) (January 28): ra11. doi:10.1126/scisignal.2004497 | en_US |
dc.identifier.issn | 1945-0877 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:32604930 | |
dc.description.abstract | Interleukin-6 (IL-6)–mediated activation of signal transducer and activator of transcription 3 (STAT3) is a mechanism by which chronic inflammation can contribute to cancer and is a common oncogenic event. We discovered a pathway, the loss of which is associated with persistent STAT3 activation in human cancer. We found that the gene encoding the tumor suppressor microRNA miR-146b is a direct STAT3 target gene, and its expression was increased in normal breast epithelial cells but decreased in tumor cells. Methylation of the miR-146b promoter, which inhibited STAT3-mediated induction of expression, was increased in primary breast cancers. Moreover, we found that miR-146b inhibited nuclear factor κB (NF-κB)–dependent production of IL-6, subsequent STAT3 activation, and IL-6/STAT3–driven migration and invasion in breast cancer cells, thereby establishing a negative feedback loop. In addition, higher expression of miR-146b was positively correlated with patient survival in breast cancer subtypes with increased IL6 expression and STAT3 phosphorylation. Our results identify an epigenetic mechanism of crosstalk between STAT3 and NF-κB relevant to constitutive STAT3 activation in malignancy and the role of inflammation in oncogenesis. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | American Association for the Advancement of Science (AAAS) | en_US |
dc.relation.isversionof | doi:10.1126/scisignal.2004497 | en_US |
dc.relation.hasversion | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233120/ | en_US |
dash.license | LAA | |
dc.title | STAT3 Induction of miR-146b Forms a Feedback Loop to Inhibit the NF- B to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes | en_US |
dc.type | Journal Article | en_US |
dc.date.updated | 2014-08-08T14:09:39Z | |
dc.description.version | Accepted Manuscript | en_US |
dc.rights.holder | 21. Xiang M, Birkbak NJ, Vafaizadeh V, Walker SR, Yeh JE, Liu S, Kroll Y, Boldin M, Taganov K, Groner B, Richardson AL, Frank DA. | |
dc.relation.journal | Science Signaling | en_US |
dash.depositing.author | Frank, David Alan | |
dc.date.available | 2017-04-27T19:25:53Z | |
dc.identifier.doi | 10.1126/scisignal.2004497 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Yeh, Jennifer | |
dash.contributor.affiliated | Xiang, Michael | |
dash.contributor.affiliated | Liu, Suhu | |
dash.contributor.affiliated | Birkbak, N | |
dash.contributor.affiliated | Frank, David | |
dash.contributor.affiliated | Walker, Sarah | |
dash.contributor.affiliated | Richardson, Andrea | |