The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway
Autor: | Hourong Peng, Suna Cai, Qiuping Huang, Wei Zhang, Yujun Zhang, Qi Li, Mengzhao Zhang, Ningjing Liu, Ting Huyan |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Proliferation index Caspase 1 Apoptosis Receptors Cell Surface Caspase 3 Exosomes Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Cyclin D1 Cell Movement Cell Line Tumor microRNA Genetics Animals Humans Genes Tumor Suppressor Wnt Signaling Pathway Molecular Biology Mice Inbred BALB C Chemistry Wnt signaling pathway Xenograft Model Antitumor Assays MicroRNAs 030104 developmental biology Urinary Bladder Neoplasms Catenin Cancer research 030217 neurology & neurosurgery Biotechnology |
Zdroj: | The FASEB Journal. 34:12177-12196 |
ISSN: | 1530-6860 0892-6638 |
DOI: | 10.1096/fj.202000347r |
Popis: | miR-375-3p is a significantly downregulated miRNA in bladder cancer (BC). However, its role in BC regulation is still unclear. In this study, we reported that miR-375-3p overexpression inhibited proliferation and migration and promoted apoptosis in BC cells. Frizzled-8 (FZD8) gene is identified as the direct miR-375-3p targeting gene. miR-375-3p blocks the Wnt/β-catenin pathway and downstream molecules Cyclin D1 and c-Myc by inhibiting the expression of FZD8 directly, it could increase caspase 1 and caspase 3 expression and promote T24 cell apoptosis as well. miR-375-3p also showed a significant inhibitory effect in vivo in bladder tumor-bearing nude mice, as demonstrated by the reduced tumor volume and Ki67 proliferation index in tumor tissue. Collectively, miR-375-3p is a suppressor of BC that inhibits proliferation and metastasis, and promotes apoptosis in BC cells as well as suppresses tumor growth in a T24 xenograft mouse model, which could be used as a potential therapeutic approach for BC in future. |
Databáze: | OpenAIRE |
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