title: CCL18-mediated down-regulation of miR98 and miR27b promotes breast cancer metastasis.
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.
authors.affiliation: Breast Tumor Center, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, People's Republic of China.|Diagnosis and Treatment Center of Breast Diseases, Shantou Hospital, SunYat-Sen University, Shantou, Guangdong Province, People's Republic of China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, No. 2 Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Chen
authors.affiliation: 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.|Breast Tumor Center, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Yandang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Breast Tumor Center, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, People's Republic of China.|Department of Oncology and Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People's Republic of China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Zhao
authors.affiliation: 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.|Breast Tumor Center, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Breast Tumor, The Third Hospital of Nanchang, Nanchang City, Jiangxi Province, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, No. 2 Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Kailian
authors.initials: K
authors.lastname: Hou
authors.affiliation: 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.|Breast Tumor Center, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 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.|Breast Tumor Center, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Fengxi
authors.initials: F
authors.lastname: Su
authors.affiliation: Department of Medical Oncology, No. 2 Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Jingqi
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.|Breast Tumor Center, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Erwei
authors.initials: E
authors.lastname: Song
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015398:Signal Transduction
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC; C531388:MIRN27 microRNA, human; C546084:MIRN98 microRNA, human; D035683:MicroRNAs
keywords: CCL18; breast cancer; miR27b; miR98; microRNA; tumor associated macrophages