Research Papers:

CCL18-mediated down-regulation of miR98 and miR27b promotes breast cancer metastasis

Xiaorong Lin, Lijun Chen, Yandang Yao, Ruihua Zhao, Xiuying Cui, Jun Chen, Kailian Hou, Mingxia Zhang, Fengxi Su, Jingqi Chen and Erwei Song _

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Oncotarget. 2015; 6:20485-20499. https://doi.org/10.18632/oncotarget.4107

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Xiaorong Lin2,4,*, Lijun Chen3,*, Yandang Yao1,2,*, Ruihua Zhao2,6,*, Xiuying Cui1,2, Jun Chen5, Kailian Hou3, Mingxia Zhang1,2, Fengxi Su1,2, Jingqi Chen3 and Erwei Song1,2

1 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China

2 Breast Tumor Center, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, People’s Republic of China

3 Department of Medical Oncology, No. 2 Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China

4 Diagnosis and Treatment Center of Breast Diseases, Shantou Hospital, SunYat-Sen University, Shantou, Guangdong Province, People’s Republic of China

5 Department of Breast Tumor, The Third Hospital of Nanchang, Jiangxi Province, People’s Republic of China

6 Department of Oncology and Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People’s Republic of China

* These authors have contributed equally to this work

Correspondence to:

Erwei Song, email:

Jingqi Chen, email:

Keywords: miR98; miR27b; microRNA; CCL18; tumor associated macrophages; breast cancer

Received: December 12, 2014 Accepted: April 20, 2015 Published: May 12, 2015


Our previous work has indicated that CCL18 secreted by tumor-associated macrophages (TAMs) promotes breast cancer metastasis, which is associated with poor patient prognosis. However, it remains unclear whether microRNAs (miRNAs), which may modulate multiple cellular pathways, are involved in the regulation of CCL18 signaling and the ensuing metastasis of breast cancer. In this study, we demonstrated that CCL18 reduces miR98 and miR27b expression via the N-Ras/ERK/PI3K/NFκB/Lin28b signaling pathway, while down-regulation of these mRNAs feedbacks to increase N-Ras and Lin28b levels. This cascade of events forms a positive feedback loop that sustains the activation of CCL18 signaling. More importantly, reduction in miR98 and miR27b enhances the epithelial-mesenchymal transition (EMT) of breast cancer cells, and thus promotes breast cancer metastasis. These findings suggest that down-regulation of miR98 and miR27b promotes CCL18-mediated invasion and migration of breast cancer cells.

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