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  • Title: Cervical Cancer Cells-Secreted Exosomal microRNA-221-3p Promotes Invasion, Migration and Angiogenesis of Microvascular Endothelial Cells in Cervical Cancer by Down-Regulating MAPK10 Expression.
    Author: Zhang L, Li H, Yuan M, Li M, Zhang S.
    Journal: Cancer Manag Res; 2019; 11():10307-10319. PubMed ID: 31849520.
    Abstract:
    PURPOSE: Cervical cancer (CC) is recognized as a common cancer with a high risk worldwide. Exosomal microRNAs (miRNAs) have received attention for their increasing potentials in CC therapy. In this study, we identify the involvement of miR-221-3p in CC progression by affecting angiogenesis of microvascular endothelial cells (MVECs). METHODS: Microarray-based gene expression profiling was conducted to retrieve the differentially expressed genes in CC. The expression patterns of miR-221-3p were measured by RT-qPCR, while Western blot analysis and RT-qPCR were performed to determine the expression of MAPK10 in the CC tissues and cells, followed by verification of the interaction between miR-221-3p and MAPK10 using dual luciferase reporter gene assay. Then the effects of miR-221-3p and MAPK10 on cell activities were assessed through gain- and loss-of-function experiments in CC. Subsequently, the impact of exosomal miR-221-3p on MVEC proliferation, migration, invasion and angiogenesis was examined after exosomal isolation from CC cells and co-cultured with MVECs. RESULTS: Gene expression profile showed that MAPK10 might participate in CC with a low expression. Moreover, miR-221-3p was highly expressed and MAPK10 was poorly expressed in CC tissues and cells. It was observed that miR-221-3p targeted MAPK10. Depletion of miR-221-3p blocked the cell proliferation, invasion and migration in CC by up-regulating MAPK10. Moreover, CC cells-derived exosomes carrying miR-221-3p accelerated MVEC proliferation, invasion, migration and angiogenesis in CC by regulating MAPK10. CONCLUSION: CC cells-derived exosomes harboring miR-221-3p enhanced MVEC angiogenesis in CC by decreasing MAPK10.
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