miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer |
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| Authors: | T Chiyomaru H Enokida S Tatarano K Kawahara Y Uchida K Nishiyama L Fujimura N Kikkawa N Seki and M Nakagawa |
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| Institution: | 1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan;2Kawahara Nephro-urology Clinic, Kagoshima, Japan;3Biomedical Research Center, Chiba University, Chiba, Japan;4Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan |
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| Abstract: | Background: We have recently identified down-regulated microRNAs including miR-145 and miR-133a in bladder cancer (BC). The aim of this study is to determine the genes targeted by miR-145, which is the most down-regulated microRNA in BC.Methods: We focused on fascin homologue 1 (FSCN1) from the gene expression profile in miR-145 transfectant. The luciferase assay was used to confirm the actual binding sites of FSCN1 mRNA. Cell viability was evaluated by cell growth, wound-healing, and matrigel invasion assays. BC specimens were subjected to immunohistochemistry of FSCN1 and in situ hybridisation of miR-145.Results: The miR-133a as well as miR-145 had the target sequence of FSCN1 mRNA by the database search, and both microRNAs repressed the mRNA and protein expression of FSCN1. The luciferase assay revealed that miR-145 and miR-133a were directly bound to FSCN1 mRNA. Cell viability was significantly inhibited in miR-145, miR-133a, and si-FSCN1 transfectants. In situ hybridisation revealed that miR-145 expression was markedly repressed in the tumour lesion in which FSCN1 was strongly stained. The immunohistochemical score of FSCN1 in invasive BC (n=46) was significantly higher than in non-invasive BC (n=20) (P=0.0055).Conclusion: Tumour suppressive miR-145 and miR-133a directly control oncogenic FSCN1 in BC. |
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| Keywords: | FSCN1 microRNA miR-145 miR-133a bladder cancer |
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