CCL18-mediated Down-regulation of MiR98 and MiR27b Promotes Breast Cancer Metastasis

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Aug 6

PMID 26244871

Citations 24

Authors

Xiaorong Lin

Lijun Chen

Yandang Yao

Ruihua Zhao

Xiuying Cui

Jun Chen

Kailian Hou

Mingxia Zhang

Fengxi Su

Jingqi Chen

Erwei Song

Affiliations

Soon will be listed here.

Abstract

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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