The strength and duration of NF-kB signaling is tightly controlled at multiple levels under physiologic conditions, but the mechanism underlying constitutive activation of the NF-kB pathway in cancer remains unclear. In this study, we investigated miRNA-mediated regulation of the NF-kB cascade in breast cancer. We report that miR-892b expression was significantly downregulated in human breast cancer specimens and correlated with poor patient survival. Overexpression of miR-892b in breast cancer cells significantly decreased tumor growth, metastatic capacity, and the ability to induce angiogenesis, whereas miR-892b depletion enhanced these properties, in vitro and in vivo. Furthermore, we demonstrate that miR-892b attenuated NF-kB signaling by directly targeting and suppressing multiple mediators of NF-kB, including TRAF2, TAK1, and TAB3, and thus, miR-892b silencing in breast cancer cells sustains NF-kB activity. Moreover, miR-892b downregulation was attributed to aberrant hypermethylation of its promoter. Taken together, our results provide insight into a new mechanism by which NF-kB signaling becomes constitutively activated in breast cancer and suggest a tumor-suppressive role for miR-829b, prompting further investigation into miRNA mimics for cancer therapy.
The use of decision aids in breast reconstruction surgery may help decrease decisional conflict and regret through promoting improved information sharing and shared decision making, which are highly important in this particular setting, patient population, and in our move toward greater patient-centered care.
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