1. 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
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Zhang L, Li H, Yuan M, Li M, and Zhang S
- Subjects
cervical cancer ,microvascular endothelial cells ,exosomes ,microrna-221-3p ,mitogen-activated protein kinase 10 ,angiogenesis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Lu Zhang,* Huihui Li,* Ming Yuan, Mingbao Li, Shuquan Zhang Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuquan ZhangDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No.107 Wenhua West Road, Jinan, Shandong 250012, People’s Republic of ChinaTel +86 185 6008 1932Email zhangshuquan0326@126.comPurpose: 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.Keywords: cervical cancer, microvascular endothelial cells, exosomes, microRNA-221-3p, mitogen-activated protein kinase 10, angiogenesis
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- 2019