Lili Jiang1,2, Liang Yu3, Xin Zhang2, Fangyong Lei2, Lan Wang4, Xiangxia Liu5, Shu Wu2, Jinrong Zhu6, Geyan Wu6, Lixue Cao6, Aibin Liu6, Libing Song2,*, and Jun Li6,*
Author Affiliations1Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong, China.
2State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Centre, Sun Yat-sen University, Guangzhou, Guangdong, China.
3Department of Vascular and Breast Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
4Department of Pathogen Biology and Immunology, School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
5Department of Plastic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
6Program of Cancer Research, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
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:firstname.lastname@example.org; or Jun Li, email@example.com
L. Jiang and L. Yu contributed equally to this article.
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