Lili Jiang^1,2, Liang Yu³, Xin Zhang², Fangyong Lei², Lan Wang⁴, Xiangxia Liu⁵, Shu Wu², Jinrong Zhu⁶, Geyan Wu⁶, Lixue Cao⁶, Aibin Liu⁶, Libing Song^2,*, and Jun Li^6,*

Author Affiliations

↵*Corresponding Authors:
Libing Song, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China. Phone: 86-20-87343187; Fax: 86-20-87335828; E-mail:songlb@sysucc.org.cn; or Jun Li, lijun37@mail.sysu.edu.cn

L. Jiang and L. Yu contributed equally to this 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.

The copyright reseverd by Cancer Res; 76(5); 1101–11. ©2016 AACR. Please log on Cancer Res to view the full text. http://cancerres.aacrjournals.org/content/76/5/1101.abstract