Let-7a mimic attenuates CCL18 induced breast cancer cell metastasis through Lin 28 pathway |
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| Institution: | 1. Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, 453100, Xinxiang, PR China;2. Department of Pathophysiology, Xinxiang Medical University, 453003, Xinxiang, PR China;1. Department of Clinical and Experimental Medicine, University of Messina, Italy;2. Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Italy;3. Department of Statistics, University of Messina, Italy;4. Department of Biomedical Sciences and of Morphologic and Functional Images, University of Messina, Italy;1. Clinical Trials Center, Cardiovascular Research Foundation, New York, New York;2. Department of Cardiology, Asan Medical Center, Seoul, South Korea;3. Division of Cardiology, Columbia University Medical Center, New York, New York;4. Department of Cardiology, Shaare Zedek Medical Center, Jerusalem, Israel;5. Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York;6. Antwerp Cardiovascular Center, ZNA Middelheim, Antwerp, Belgium;7. Thoraxcenter, Rotterdam, The Netherlands;1. INSERM UMR 1178, University Paris Sud, Service de Psychiatrie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France;2. INSERM 1185, Faculty of Medicine Paris Sud, University Paris-Saclay, Le Kremlin-Bicêtre, F-94276, France, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Le Kremlin Bicêtre F-94275, France;3. INSERM UMR 1178, Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, Département d’addictologie, Assistance Publique-Hôpitaux de Paris, Villejuif 94800, France;4. INSERM UMR 1178, CESP, Département de Biostatistiques, University Paris Sud, Hôpital Paul Brousse, Assistance Publique Hôpitaux de Paris, 94400 Villejuif, France;5. University Paris Sud, EA 4123, Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France, University Paris-Sud, EA4123 Chatenay-Malabry, France;6. Endocrinology Unit, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Paris, France;7. Sobonne Universities, University Paris 6, INSERM UMR S_938, Centre de Recherche Saint-Antoine, Paris, France;1. Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan;2. Faculty of Medical Engineering, Suzuka University of Medical Science, 1001-1, Kishioka-cho, Suzuka, Mie 510-0293, Japan;3. Department of Biochemistry, Mie Prefectural College of Nursing, 1-1-1 Yumegaoka, Tsu, Mie 514-0116, Japan;4. Faculty of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3, Minamitamagaki-cho, Suzuka, Mie 513-8679, Japan;1. Department of Urology, University Hospital, Eberhard-Karls-University, Tuebingen, Germany;2. Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada |
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| Abstract: | BackgroundMicroRNAs are believed to influence breast cancer cell tumorgenicity by interacting with the production of tumor associated macrophages. At this stage, this hypothesis lacks sufficient empirical evidence. Our study is an investigation of the effects of let-7a on the function of human breast cancer cell lines that had undergone chemokine ligand 18 (CCL18) stimulation.MethodsTwo breast cancer cell lines MDA-MB-231 and MCF-7 were transfected with let-7a mimics with or without CCL18 simulation. The expression level of let-7a was evaluated with qRT-PCR. Our study examined cell proliferation, migration and cell cycles following let-7a treatment. The predicted target of let-7a was identified and confirmed in vitro by a dual luciferase reporter system. The associations between let-7a, CCL18 and target gene expression were evaluated using RT-PCR and the Western blotting method.ResultsThe downregulated expression level of let-7a was observed in both breast cancer cell lines. When compared to the control and CCL18 stimulation groups, cell proliferation and migration in MDA-MB-231 and MCF-7 cells were significantly inhibited by let-7a. Furthermore, the cell cycle was dramatically blocked at the G2/M phase. The luciferase reporter identified Lin28 as the direct binding target of let-7a in both breast cancer cell lines.ConclusionUpregulation of let-7a carries the potential to reverse CCL18 induced cell proliferation and migration alteration in breast cancer cells by regulating Lin28 expression. Our results provided evidence which suggests the use of let-7a as a therapeutic agent in the treatment of breast cancer. |
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| Keywords: | Breast cancer MicroRNAs Tumor associated macrophages Cell cycle Cell migration |
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