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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
MiR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness
Oncogene, Volume 29, No. 50, Year 2010
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Description
Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell-cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3′UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy. © 2010 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
Götte, Martin
Germany, Munster
Universitätsklinikum Münster
Mohr, Caroline F.
Germany, Munster
Universitätsklinikum Münster
Koo, Chuay Yeng
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Stock, Christian Martin
Germany, Munster
Universitätsklinikum Münster
Vaske, A. K.
Germany, Munster
Universitätsklinikum Münster
Viola, Manuela
Germany, Munster
Universitätsklinikum Münster
Ibrahim, Sherif Abdelaziz
Germany, Munster
Universitätsklinikum Münster
Egypt, Giza
Faculty of Science
Peddibhotla, Swetha S.D.
Germany, Munster
University of Münster
Teng, Yvonne Hui Fang
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Low, Jiayi
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Ebnet, Klaus
Germany, Munster
University of Münster
Kiesel, Ludwig
Germany, Munster
Universitätsklinikum Münster
Yip, George Wai Cheong
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Statistics
Citations: 212
Authors: 13
Affiliations: 4
Identifiers
Doi:
10.1038/onc.2010.386
ISSN:
09509232
e-ISSN:
14765594
Research Areas
Cancer