title: miR-143 suppresses epithelial-mesenchymal transition and inhibits tumor growth of breast cancer through down-regulation of ERK5.
abstract: Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development of cancer invasion and metastasis. Many studies have significantly enhanced the knowledge on EMT through the characterization of microRNAs (miRNAs) influencing the signaling pathways and downstream events that define EMT on a molecular level. In this study, we found that miR-143 suppressed EMT. Up-regulating miR-143 enhanced E-cadherin-mediated cell-cell adhesion ability, reduced mesenchymal markers, and decreased cell proliferation, migration, and invasion in vitro. In vivo, the xenograft mouse model also unveiled the suppressive effects of miR-143 on tumor growth. Additionally, we demonstrated that up-regulating extracellular signal regulated kinase 5 (ERK5) was associated with poor prognosis of breast cancer patients. Moreover, we observed an inverse correlation between miR-143 and ERK5 in breast cancer tissues. miR-143 directly targeted seed sequences in the 3'-untranslated regions of ERK5. Furthermore, we revealed that the downstream molecules of glycogen synthase kinase 3 beta (GSK-3β)/Snail signaling were involved in EMT and modulated by ERK5. In summary, our findings demonstrated that miR-143 down-regulated its target ERK5, leading to the suppression of EMT induced by GSK-3β/Snail signaling of breast cancer. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, Shandong Province, P.R. China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhai
authors.affiliation: Department of Pathology, Afflidated Hospital of Weifang Medical University, Weifang, Shandong Province, P.R. China.
authors.forename: Chuanxiang
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, Shandong Province, P.R. China.
authors.forename: Wentong
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology, Weifang Medical University, Weifang, Shandong Province, P.R. China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Medical Biology, Weifang Medical University, Weifang, Shandong Province, P.R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics*; D011379:Prognosis; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D048054:Mitogen-Activated Protein Kinase 7
keywords: EMT; ERK5; GSK-3β; breast cancer; miR-143