title: MicroRNA-182 drives colonization and macroscopic metastasis via targeting its suppressor SNAI1 in breast cancer.
abstract: Metastasis is a multi-step process. Tumor cells occur epithelial-mesenchymal transition (EMT) to start metastasis, then, they need to undergo a reverse progression of EMT, mesenchymal-epithelial transition (MET), to colonize and form macrometastases at distant organs to complete the whole process of metastasis. Although microRNAs (miRNAs) functions in EMT process are well established, their influence on colonization and macrometastases formation remains unclear. Here, we established an EMT model in MCF-10A cells with SNAI1 overexpression, and characterized some EMT-related microRNAs. We identified that miR-182, which was directly suppressed by SNAI1, could enable an epithelial-like state in breast cancer cells in vitro, and enhance colonization and macrometastases in vivo. Subsequent studies showed that miR-182 exerted its function through targeting its suppressor SNAI1. Moreover, higher expression level of miR-182 was detected in metastatic lymph nodes, compared with paired primary tumor tissues. In addition, the expression level of miR-182 was negatively correlated with that of SNAI1 in these clinical specimens. Taking together, our findings describe the role of miR-182 in colonization and macrometastases in breast cancer for the first time, and provide a promise for diagnosis or therapy of breast cancer metastasis.
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.|State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xukun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Xiaoshuan
authors.initials: X
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Bangrong
authors.initials: B
authors.lastname: Cao
authors.affiliation: Department of Breast Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Baona
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Breast Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Da
authors.initials: D
authors.lastname: Pang
authors.affiliation: State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D000071250:Snail Family Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors
keywords: SNAI1; breast cancer; colonization; metastasis; miR-182