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posted on 2023-03-30, 23:44 authored by Lili Jiang, Liang Yu, Xin Zhang, Fangyong Lei, Lan Wang, Xiangxia Liu, Shu Wu, Jinrong Zhu, Geyan Wu, Lixue Cao, Aibin Liu, Libing Song, Jun Li Supplementary Figure 6. Downregulation of miR-892b is attributed to hypermethylation of its promoter.
Funding
Ministry of Science and Technology of China
Distinguished Young Scholar of Guangdong Province, China
GDUPS (2012); Natural Science Foundation of China
Science and Technology of Guangdong Province
Guangdong special Support program
Guangzhou scholars research projects of Guangzhou municipal colleges and universities
Pearl River projects (Young Talents of Science and Technology) in Guangzhou
Foundation of Key Laboratory of Gene Engineering of the Ministry of Education
History
ARTICLE ABSTRACT
The strength and duration of NF-κB signaling is tightly controlled at multiple levels under physiologic conditions, but the mechanism underlying constitutive activation of the NF-κB pathway in cancer remains unclear. In this study, we investigated miRNA-mediated regulation of the NF-κB 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-κB signaling by directly targeting and suppressing multiple mediators of NF-κB, including TRAF2, TAK1, and TAB3, and thus, miR-892b silencing in breast cancer cells sustains NF-κB 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-κB 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. Cancer Res; 76(5); 1101–11. ©2016 AACR.
